# Endoplasmic reticulum proteostasis contributes to shape plant immunity: Perspectives from plant and pathogen sides

Tania Marzari, Emma Poilvert, Cécile Blanchard, Nathalie Leborgne-Castel, Benoit Poinssot, Jean-Luc Cacas, Olivier Lamotte, Mathieu Gayral

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## ► To cite this version:

Tania Marzari, Emma Poilvert, Cécile Blanchard, Nathalie Leborgne-Castel, Benoit Poinssot, et al. "Endoplasmic reticulum proteostasis contributes to shape plant immunity: Perspectives from plant and pathogen sides." Current Plant Biology, 2025, 44, pp.100552. 10.1016/j.cpb.2025.100552. hal-05344609

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Submitted on 3 Nov 2025

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# Endoplasmic reticulum proteostasis contributes to shape plant immunity: Perspectives from plant and pathogen sides

Tania Marzari<sup>a,1,2</sup>, Emma Poilvert<sup>a,1,3</sup>, Cécile Blanchard<sup>a,9</sup>, Nathalie Leborgne-Castel<sup>a,4</sup>, Benoit Poinssot<sup>a,5</sup>, Jean-Luc Cacas<sup>b,6</sup>, Olivier Lamotte<sup>a,c,7</sup>, Mathieu Gayral<sup>a,*8</sup> <sup>†</sup>

## ARTICLE INFO

### Keywords:

UPR

ER-QC

ER stress

Protein homeostasis

Plant immunity

## ABSTRACT

The endoplasmic reticulum (ER) is the gate to the secretory pathway for at least one third of the newly synthesized proteins. Its proper function is essential for keeping cellular homeostasis during plant development and responses to environmental cues. Plants have evolved a wide set of cellular and molecular systems that allow to maintain a delicate balance between protein synthesis, folding, and degradation. Among these, ER quality control (ER-QC) plays key roles. However, biotic and abiotic stresses can disrupt this balance, leading to protein homeostasis disturbance and ER stress. This can lead to programmed cell death under acute conditions. To cope with this, plant cells activate the unfolded protein response (UPR) to restore ER and cellular homeostasis. Increasing evidence shows that UPR signaling has a significant impact on plant immunity. This supports the concept of ER stress-mediated immunity (ERSI), in which the UPR drives plant immunity. In contrast, pathogen effectors can manipulate host protein homeostasis to facilitate infection. In addition, recent results reveal that the ER proteostasis of plant-interacting pathogens is involved in pathogenicity. In this review, we discuss the latest findings on ER protein homeostasis, with a particular focus on its interplay with plant immunity. We also explore how pathogens manipulate the ER proteostasis of the host cell and propose a model where both partners exploit each other's ER proteostasis for their own advantage.

## 1. Introduction

Plants have evolved diverse mechanisms to tolerate abiotic and biotic stresses through physiological, biochemical and molecular adaptations, ensuring their survival. As one of the largest and most functionally significant structure in eukaryotic cells, the endoplasmic reticulum (ER) acts as a central hub for the secretory pathway. One third of newly

synthesized proteins co-translationally enter the ER in an unfolded state, and subsequently undergo post-translational modifications (like N-linked glycosylation) to achieve their proper folding and functionality [1]. This process is constantly supervised by the ER-mediated quality control (ER-QC), a system that supports protein folding and monitors the protein integrity by the activity of numerous ER-resident chaperons, co-chaperons, and enzymes. If protein folding attempts fail or if the

<footnote><sup>a</sup> Université Bourgogne Europe, Institut Agro, INRAE, Agroécologie, Dijon 21000, France</footnote>

<footnote><sup>b</sup> Institut Jean-Pierre Bourgin, INRAE, AgroParisTech, Université Paris-Saclay, Versailles, France</footnote>

<footnote><sup>c</sup> Université Bourgogne Europe, Institut Agro, CNRS, INRAE, UMR CSGA, Dijon 21000, France</footnote>

<footnote>* Corresponding author.</footnote>

<footnote>E-mail addresses: tania.marzari@inrae.fr (T. Marzari), emma.poilvert@inrae.fr (E. Poilvert), cecile.blanchard@u-bourgogne.fr (C. Blanchard), nathalie.leborgne-castel@inrae.fr (N. Leborgne-Castel), benoit.poinssot@inrae.fr (B. Poinssot), jean-luc.cacas@inrae.fr (J.-L. Cacas), olivier.lamotte@inrae.fr (O. Lamotte), mathieu.gayral@inrae.fr (M. Gayral).</footnote>

<footnote n="1">¹ These authors contributed equally to this work</footnote>

<footnote n="2">² https://orcid.org/0009-0006-5847-8475</footnote>

<footnote n="3">³ https://orcid.org/0009-0005-1502-9468</footnote>

<footnote n="4">⁴ https://orcid.org/0000-0001-8756-4463</footnote>

<footnote n="5">⁵ https://orcid.org/0000-0001-5890-4318</footnote>

<footnote n="6">⁶ https://orcid.org/0000-0002-8961-4505</footnote>

<footnote n="7">⁷ https://orcid.org/0000-0002-3721-3769</footnote>

<footnote n="8">⁸ https://orcid.org/0000-0001-5760-1622</footnote>

<footnote n="9">⁹ https://orcid.org/0009-0006-0935-9361</footnote>
native conformation cannot be reached, misfolded proteins are
retro-translocated from ER lumen to cytoplasm where they are degraded
by the ubiquitin/proteasome system in a process dubbed ER-associated
degradation (ERAD) [2,3]. The finely tuned balance between protein
folding and degradation of misfolded/unfolded proteins is tightly
regulated to maintain ER protein homeostasis. This ensures cellular
function and adaptability under developmental and stress conditions.
Adverse environmental conditions, including infection, can intensify the
workload of the ER beyond its capacity. As a result, the protein folding
machinery becomes overwhelmed, leading to the accumulation of mis-
folded/unfolded proteins in the ER lumen, and causing the so-called
ER-stress [2]. Consequently, stressed cells activate the unfolded pro-
tein response (UPR). This signaling pathway is a homeostatic response
designed to align the ER protein-folding and degradation capacities with
the cell demand [4]. In plants, the UPR is primarily mediated by two
distinct signaling arms, which are partially conserved across eukaryotic
cells and constitute the 'canonical UPR'. Alongside this pathway, alter-
native factors, specific to the plant kingdom also contribute to UPR
signaling and are referred to as the 'non-canonical UPR'. When properly
managed, mild ER-stress can be mitigated, allowing organelle recovery.
By contrast, prolonged or acute ER stress can trigger autophagy, pro-
grammed cell death (PCD), or even the death of the entire plant [5,6].

Beyond maintaining cellular homeostasis, proteostasis also serves as a key regulator of plant immunity, providing the foundation for effective defense outcomes. To face biotic stress, plants have developed multi-layered, innate immune responses to detect and cope with pathogens [7,8]. The first layer of defense relies on microbial- or pathogen-associated molecular patterns (MAMPs or PAMPs) as well as damage-associated molecular patterns (DAMPs) recognition via cell surface pattern recognition receptors (PRRs). This induces a signaling cascade through reactive oxygen species (ROS) production, Ca²⁺ influx, and activation of mitogen-activated protein kinases (MAPKs) leading to defense onset. These defenses, based on pattern recognition, are known as Pattern-triggered immunity (PTI) and notably lead to cell wall fortification, production of phytoalexins, and secretion of pathogenesis-related (PR) proteins [9]. In response, pathogens have developed a strategy to escape the PTI by secreting effectors to suppress host immunity, in the so-called effector-triggered susceptibility (ETS) [10,11]. Consequently, plants have developed a second layer of defense based on effector recognition by nucleotide-binding domain leucine-rich repeat containing receptors (NLR). This defense mechanism, named effector-triggered immunity (ETI), is based on recognition of pathogen avirulence effectors (Avr) and triggering a Hypersensitive Response (HR) [12]. The molecular dialog between ETS and ETI places a selective pressure on both interacting partners that led to the seminal 'zigzag' model proposed by Jones and Dangl [7,10,13].

Over the past decades, numerous studies have started investigating
the role of ER stress and the subsequent activation of the UPR during
plant-pathogen interactions, mainly in the plant model *Arabidopsis*
*thaliana* and during interactions with viruses [14,15]. These previous
studies underscore the significant impact of UPR signaling on plant
immunity, laying the foundations of ER stress-mediated immunity
(ERSI), which is herein defined as the immune responses mediated by
UPR signaling pathway. Depending on the lifestyle of pathogen chal-
lenging the host plant, UPR and ER-QC are either involved in the plant
defense response helping to stop invaders' ingress or be hijacked by
them to facilitate host cell infection. In both cases, ER proteostasis and
its regulatory mechanisms remain crucial for determining the outcome
of the infection, i.e. susceptibility or (quantitative) resistance. In this
review, we sum up the latest discoveries concerning ER proteostasis and
its regulation during plant interactions with bacterial, fungal and
oomycetal pathogens. We first describe the role of the ER-QC system in
regulating ER proteostasis in plant cells, highlighting their components,
primary functions, and their involvement during biotic stress. We then
explore how the UPR safeguards proteostasis and immunity through
ERSI, while pathogens can hijack it to lower plant immunity and favor

their own growth by hijacking the plant immunity. Finally, we focus on
ER proteostasis of pathogens during the infection process and highlight
that ER proteostasis plays a key role in both interacting partners.

## 2. ER-QC: gatekeepers of protein quality

The lumen of the ER provides a specialized environment that pro-
motes post-translational modifications and folding of proteins following
the anterograde transport routes, including apoplastic, vacuole storage
or transmembrane proteins. ER-QC plays an essential role in this pro-
cess, facilitating proper folding and preventing the accumulation of
misfolded/unfolded proteins. In plants, ER molecular chaperones
include BiP (Binding immunoglobulin Protein), ERdj3 (ER-localized
DnaJ-3), SDF2 (STROMAL CELL-DERIVED FACTOR 2), PDI (Protein
Disulfide Isomerase), as well as two families of lectin-type proteins,
namely the calreticulin (CRT) and the calnexin (CNX) (Fig. 1). Proteins
taking the anterograde pathway are commonly post-translationally
modified in the ER lumen, which includes glycosylation that partici-
pates in protein quality control. This process begins as the nascent
protein enters the ER through the universally conserved heterotrimeric
protein-conducting channel SEC61. A preformed oligosaccharide is then
transferred in bloc by the oligosaccharyltransferase (OST) complex to an
asparaginyl (N) residue of the nascent protein within a consensus NXS/T
motif. It is important to note that both SEC61 and OST are poorly
characterized in plants, but purification of OST complex from A. thaliana
has revealed homologs of animal and fungal proteins with similar
functions [16].

The first chaperone that a newly synthesized protein encounters
upon translocation into the ER lumen is BiP, a well-characterized and
abundant member of the Hsp70 (Heat Shock Protein 70) family [17],
which can bind to ERdj3 and SDF2 [18]. Members of the BiP family
harbor two domains, an N-terminal ATPase domain, known as the
nucleotide-binding domain (NBD) and a C-terminal substrate binding
domain (SBD). The NBD undergoes several cycles of ATP hydrolysis to
regulate substrate binding, while the SBD binds to a specific hydro-
phobic motif of nascent polypeptides [19]. BiPs follow ATP hydrolysis
cycles to bind and release proteins and are stimulated by ERdj3, which
plays an essential role in stabilizing the complex. In addition, SDF2 plays
a role in inhibiting protein aggregation. In plants, the detailed mecha-
nism of the entire binding and release process linked to protein folding
and assembly remains largely unclear. ERdj3 proteins have been char-
acterized only in *Oryza sativa*, *Nicotiana benthamiana* and *Arabidopsis
thaliana*. In *O. sativa*, the two isoforms ERdj3A and ERdj3B, bind to BIPs
and accumulate in response to ER stress [20]. All nascent polypeptides
in the ER undergo oxidative folding, a process that requires PDIs and the
sulphydryl oxidase ER OXIDOREDUCTASE-1 (ERO1). PDIs are
thioredoxin-type chaperones that promote the oxidation of dithiols
leading to the formation of disulfide bonds but also their isomerization
or reduction. ERO1 can catalyze the re-oxidation of PDI using gluta-
thione, ensuring continuous transfer of disulfides to substrate proteins
[21,22].

Two glucose (Glc) molecules from the previously transferred oligo-
saccharide are then sequentially removed by glucosidases I and II (GCSI
and GCSII), generating proteins with monoglucosylated glycans
(GlcNAc~2~Man~9~Glc~1~) [23]. This N-glycan modification serves as a recog-
nition signal that drives client proteins into the CNX/CRT
protein-folding cycle. The lectin chaperone CNX, anchored to the ER
membrane, and the soluble chaperone CRT allow their proper folding
[24]. Under non-stressed conditions, subsequent removal of the
remaining glucose (from GlcNAc~2~Man~9~Glc~1~) leads to dissociation of
client proteins from CNX/CRT and their export from the ER. Despite the
assistance of those molecular chaperones, some proteins fail to fold
properly but still lose their single, terminal glucose residue. These mis-
folded proteins are recognized by UGGT (UDP-glucose glycoprotein
glycosyltransferase) that adds back a Glc residue allowing the glyco-
protein to re-associate with CNX and CRT for another round of folding. If
<figure><img src="image_4.png" /><figcaption>**Fig. 1.** Schematic representation of the plant endoplasmic reticulum quality control (ER-QC) and its involvement during interactions with various pathogens. The oligosaccharyltransferase (OST) complex transfers an oligosaccharide to a nascent protein entering the endoplasmic reticulum (ER) via the protein-conducting channel SEC61 channel. Protein folding and maturation are assisted by Binding immunoglobulin Protein (BiP), STROMAL CELL-DERIVED FACTOR 2 (SDF2), ER-localized DnaJ-3 (ERdj3), and Protein Disulfide Isomerase (PDI), helped by the sulfhydryl oxidase ER OXIDOREDUCTASE-1 (ERO1). Glucosidase I (GCSI) and glucosidase II (GCSII) remove two glucose residues before entering the folding cycle driven by calnexin (CNX) and/or calreticulin (CRT). The UDP-glucose glycoprotein glucosyltransferase (UGGT) leads to re-enter the CNX and/or CRT cycle. Persistent misfolding leads to demannosylation by α-mannosidase (MNS) and degradation through ER-Associated Degradation (ERAD). Several ER-QC components contribute to defence outcomes, promoting resistance or susceptibility to bacterial and fungal pathogens, indicated by dashed arrows.</figcaption></figure>

the protein still fails to fold correctly after multiple cycles, it is degraded via the ERAD pathway. In plants, α-mannosidase enzymes, MNS4 and MNS5, progressively trim N-glycans on misfolded proteins, targeting them for cytoplasmic degradation. This process leads to retro-translocation of such misfolded proteins to the cytoplasm and their ubiquitination for subsequent degradation by the proteasome (refer to Strasser, 2018 for further details on the ERAD pathway [3]).

Finally, the identification of ER-QC actors was primarily conducted in plant models, such as *A. thaliana*. Nevertheless, one may speculate that similar mechanisms governing both protein quality control and trafficking could be conserved across a broad spectrum of land plant species.

**3. Folding the line: The ER-QC's battle between plant immunity and pathogen hijacking**

Folding is essential to produce functional proteins, a process that is particularly crucial in plant immunity. Indeed, plant defense against pathogens involves a great variety of proteins, including PRRs or the antimicrobial PR proteins, that engage in the anterograde pathway. Proper folding of these proteins is ensured by the ER-QC system, and several studies indicate that its actors play an important role in plant immunity (Fig. 1). In the first place, mutations affecting the OST complex lead to an increased susceptibility to various pathogens. For

example, in *A. thaliana*, knock-down *hap6* (impacted in the ER-residing ribophorin *HAPLESS 6*, also named *RPN2* (*RIBOPHORIN II*)) line presents higher susceptibility to powdery and downy mildews caused by the fungus *Erysiphe cruciferarum* [25] and the oomycete *Hyaloperonospora arabidopsidis* [26], respectively.

The ER chaperones that assist folding of nascent polypeptides are likewise essential for immunity [18,27,28]. In *A. thaliana*, the *bip2* mutant is impaired in PR1 secretion, systemic acquired resistance, and ER stress tolerance [29]. Additionally, ERdj3B and SDF2 were found to play a role in PRR folding and plant resistance to pathogens. The mutants *erdj3b* and *sdf2* exhibit impaired EFR- (EF-Tu Receptor) and FLS2-(flagellin sensing 2 receptor) dependent signaling, along with increased susceptibility to bacterial speck, black spot, and grey mold diseases caused by *Pseudomonas syringae* pv. *tomato* (*Pst*) DC3000, the necrotrophic fungi *Alternaria brassicicola* and *Botrytis cinerea*, respectively [18,30]. Interestingly, in *Solanum lycopersicum* and *Glycine max*, *BiP* overexpression increases the abundance of defense proteins and phytoalexin precursors, enhances antioxidant capacity, and confers greater tolerance to *S. lycopersicum* infected by the witches' broom disease fungal agent *Moniliophthora perniciosa* (Fig. 1) [31–33]. It is noteworthy that *BiP* overexpressing lines exhibit higher salicylic acid (SA) content and accelerated HR triggered by nonhost *Pst* in *G. max* and *Nicotiana tabacum*, whereas silencing of *BiP* reduced infection in *N. tabacum* [31,32]. Finally, the early over-expression of *PDI* genes in a
*Triticum aestivum* L. resistant line infected by *Zymoseptoria tritici*, the causing agent of septoria leaf blotch, also suggests the involvement of PDI in plant immunity (Fig. 1) [34].

Accompanying the polypeptides on their route, the CNX/CRT protein-folding cycle also plays an important role in plant-pathogen interactions. Notably, it has been demonstrated in *A. thaliana* that the *crt3* mutant shows higher susceptibility to the virulent strain *Pst* DC3000 [27]. In *Solanum lycopersicum*, silencing of *CRT3a* also affects the biogenesis of the PRR Cf-4 and leads to loss of resistance against tomato leaf mold caused by *Cladosporium fulvum* [35]. On the contrary, in *A. thaliana*, the overexpression of *CRT2* results in reduced resistance to *Pst* DC3000, despite an increase in SA levels and the constitutive expression of PR1, PR2, and PR5. [36]. In *A. thaliana* and *Brassica napus*, the loss-of-function of *CRT1a* strongly reduces plant susceptibility to verticillium wilt caused by *Verticillium longisporum* [37]. In *A. thaliana*, UGGT is required for the biogenesis of the leucine-rich repeat-receptor-like kinase (LRR-RLK) SUPPRESSOR OF BIR1-1 (SOBIR1), and mutations in UGGT suppress the spontaneous cell death and constitutive defense responses induced by *H. arabidopsidis* in *bir1-1* knock-out mutant (Fig. 1) [38].

Altogether, these data indicate that the ER-QC system plays a pivotal role in plant-pathogen interactions by controlling the proper folding of

secreted defense components such as antimicrobial proteins and immunity receptors.

## 4. The canonical Unfolded Protein Response: maintaining cellular integrity under stress

The two arms of the UPR have been identified and characterized in *A. thaliana* and are described below. The first one relies on the ER-transmembrane proteins INOSITOL REQUIRING ENZYME 1 (IRE1) and the transcription factor (TF) basic LEUCINE ZIPPER 60 (bZIP60) whereas the second arm involves the ER-membrane-associated TF bZIP17 and bZIP28 (Fig. 2). Interestingly, all these proteins exhibit highly conserved functional domains with their metazoan counterparts, suggesting that the UPR is an ancient, retrograde signaling pathway that is conserved across kingdoms [2,39,40], and is hereafter referred to as the canonical UPR.

The N-terminal sensor domain of IRE1 is localized in the ER lumen, while its C-terminal kinase/endoribonuclease domain faces the cytoplasm [41]. The latter is inactive at the basal state and its activation occurs through conformational changes triggered by a lateral oligomerization in the ER membrane (Fig. 2). Several hypotheses have been proposed to explain the oligomerization of IRE1 in both yeast and

<figure><img src="image_5.png" /><figcaption>**Fig. 2.** Schematic representation of the two arms of unfolded protein response (UPR) pathways and their involvement during plant-pathogen interactions. Under endoplasmic reticulum (ER) stress conditions (Yellow lightning), the Inositol Requiring Enzyme 1 (IRE1) oligomerizes to splice the basic leucine zipper 60 (bZIP60) mRNA, whose spliced form activates UPR and ER Stress-Mediated Immunity related genes (UPR/ERSI). IRE1 oligomerization also triggers RNA degradation via Regulated IRE1-Dependent Decay (RIDD). bZIP28 and bZIP17 are released from the ER membrane, cleaved in the Golgi, and translocate to the nucleus to regulate UPR/ERSI signaling, alongside Bcl-2-associated athanogene 7 (BAG7) and the ER membrane G protein β-subunit (AGB1). The ER membrane-anchored protein Resistance to Phytophora parasitica 1 (RTP1) inhibits bZIP28 and IRE1 UPR signalling. Several UPR components act as key players in immunity, enhancing resistance or modulating susceptibility to fungal and bacterial pathogens, as indicated by dashed arrows.</figcaption></figure>
mammalian cells. However, mechanisms by which IRE1 undergoes oligomerization is still debated in plants. One model suggests that BiPs could normally be associated with IRE1, thus preventing its phosphorylation-based dimerization. Under stressful conditions, BiPs could then be sequestered by misfolded/unfolded proteins, allowing IRE1 to self-oligomerize and initiate the unconventional splicing of *bZIP60* mRNA [42,43]. A second model primarily relies on the intrinsic ability of IRE1 luminal domain to directly interact with misfolded/unfolded proteins [44]. Finally, a third model proposes that the multiple competition between misfolded proteins, BiPs, and PDI9 allows the fine-tuning of IRE1 activity, notably when PDI9 interacts with IRE1, UPR signaling is attenuated [45]. The Arabidopsis genome encodes three isoforms of IRE1, named IRE1A, IRE1B, and IRE1C [41,46]. While *IRE1A* and *IRE1B* are widely express across vegetative tissues, *IRE1C*, which code for a truncated form lacking the luminal ER domain, is mainly expressed in flowers and is only involved in gametogenesis [47, 48]. Under ER stress conditions, IRE1A and IRE1B mediate the non-conventional splicing of the mRNA of *bZIP60* [46,49]. This event results in the excision of a 23 base-pair intron causing a frameshift in the open reading frame beyond the splicing site. The unspliced *bZIP60* mRNA translation produces a transmembrane protein (bZIP60u), whereas the protein translated from the spliced form (bZIP60s) loses its transmembrane domain. Thus, under non-stressed conditions, bZIP60u localizes to the ER membrane [14] where its role in UPR signaling remains unclear. However, during ER stress conditions, bZIP60s is targeted to the nucleus where it activates UPR responsive genes. IRE1 is also involved in the degradation of mRNAs by the Regulated IRE1-Dependent Decay (RIDD) (Fig. 2) [50]. This mechanism ensures the degradation of mRNAs encoding proteins predominantly processed in the ER, thus limiting the accumulation of secreted proteins [50]. In addition, further work on the RIDD mechanism has revealed that only IRE1B degrades RNAs encoding proteins that interfere with the induction of autophagy under ER stress conditions [51].

The second arm of the UPR signaling pathway is mediated by the ER-membrane-associated TFs *bZIP17* and *bZIP28*. Under restful conditions, these TFs are anchored in the ER membrane (Fig. 2) and the luminal domain of *bZIP28* is associated with BiP [52]. However, under stressful conditions, *bZIP28* dissociates from BiP and is translocated to the Golgi apparatus where it is sequentially cleaved by resident site-1 and site-2 proteases (S1P and S2P) [53]. The *bZIP17* TF is also activated by proteolytic cleavage in the Golgi apparatus [54], but there is currently no direct evidence of *bZIP17/BiP* association and/or dissociation during ER stress. The protease release the N-terminal domains of *bZIP17/bZIP28* in the cytoplasm allowing their relocation to the nucleus where they upregulate the expression of stress-responsive genes [53,54]. The model mechanism leading to the activation of *bZIP17/bZIP28* arm in plants remain to be clarified, since S1P does not appear to be essential for activating *bZIP28* [55].

To conclude, the two arms of the canonical UPR were primarily studied in *A. thaliana* and are considered representative of the UPR signaling in plants, even though some differences exist between plants, mainly regarding the *bZIP17/28* arm, whose number of transcription factors involved, and their responses may vary depending on stress [40].

## 5. UPR and plant-pathogen interactions: in between defense and susceptibility

Like ER-QC, the UPR plays an important role during plant immunity (Fig. 2). In *A. thaliana*, the single *bzip60* mutants exhibit an increased susceptibility to the necrotrophic fungi *A. brassicicola* and *B. cinerea* and the oomycete *Phytophthora parasitica* [30,56]. Additionally, *bZIP60* appears to play a crucial role in resistance against powdery mildew since the overexpression of *Vitis vinifera* *bZIP60* in *A. thaliana* enhances resistance to *Erysiphe cichoracearum* and increases *PR1* expression [57]. In the same arm, the double *ire1a ire1b* mutants exhibit an increased susceptibility to *A. brassicicola* and *B. cinerea* [30]. Yet, genetic

inactivation of the IRE1-bZIP60 arm was found not to affect the expression of defense genes normally induced by *B. cinerea*, nor genes associated with ER stress-induced PCD [30]. Thus, suggesting an unknown mechanism of ERSI for necrotrophic fungus resistance. In *N. benthamiana*, silencing of *bZIP60* compromised defense against the nonhost pathogen *Pseudomonas cichorii* [58]. In *Nicotiana attenuata*, silencing of *IRE1-bZIP60* increased plant susceptibility to *Alternaria alternata*, pointing the role of this arm in the resistance to tobacco brown spot disease [59]. In addition, *bzip60* and *ire1a ire1b* mutants show increased susceptibility to the agent of bacterial spot, *Pseudomonas syringae* pv. *maculicola* (*Psm*), which is correlated to a reduced PR1 protein secretion in the *ire1a* single mutant [60,61]. Another study showed that the same mutants exhibit increased susceptibility to *Pst* DC3000 infection only when the plants are pre-exposed to tunicamycin treatment, which inhibits the N-glycosylation occurring within the ER, thus inducing ER stress. By contrast, Liu and coworkers (2023) [62] identified a nitrate transporter involved in tunicamycin translocation. They further showed that this chemically induced ER stress could enhance Arabidopsis resistance to a virulent strain of *Pst*, likely through the induction of PR1 expression. Combined, these studies suggest that UPR is involved in hemibiotrophic bacterial infection through the secretion of defense proteins, such as PR1.

With regards to the specific role of IRE1, it is noteworthy that many potentials and confirmed RIDD target transcripts encode proteins involved in immunity. These transcripts include those encoding the peroxidase PRX34, the lipase-like EDS1 (ENHANCED DISEASE SUSCEPTIBILITY 1), the WRKY33, WRKY53, WRKY70 and MLO4 (Mildew Resistance Locus 4) TFs, several HSP, some chitinases (including PR4), the lipid transfer protein PR14 and other PR proteins belonging to the β-glucosidase and defensin families [50,51]. In line, a recent transcriptomic dataset pointed out that chronic ER stress induced by tunicamycin in Arabidopsis seedlings leads to an enhanced expression of SA-responsive genes in both shoots and roots of *ire1a ire1b* double mutant when compared to wild type (WT) [63]. Thus, one can assume that the RIDD process could control plant defense responses, but the exact mechanisms involved remains to be elucidated.

Concerning the second arm of UPR, works on *A. thaliana* have shown that the *bzip17* mutant exhibits an increased resistance to *B. cinerea* [30], whereas the *bzip28* mutant exhibits an increased susceptibility to *Pst* DC3000 and *P. parasitica* [56,64]. Moreover, in *A. thaliana*, the double mutant *bzip28 bzip60* exhibits larger symptoms of eyespot disease due to infection by *Drechslera gigantea* [65]. Although the molecular mechanisms linked to ERSI are still not delineated, it is noteworthy that induction of the UPR signaling by tunicamycin leads to ectopic lignin deposition, which is impaired in the *bzip28 bzip60* double mutant [66]. Lignin deposition acts as a physical barrier, preventing the spread of invading avirulent pathogens and restricting pathogen spatial motility [67].

Overall, these data highlight that the canonical UPR is a key player in plant immunity except for *bZIP17*, which acts as a susceptibility factor in *A. thaliana* facing *B. cinerea* ([30], Fig. 2).

## 6. Non-canonical ER stress responses in plant defense: the second line is just as important

In plants, the non-canonical ER stress responses refer to mechanisms that go beyond the canonical well-documented UPR signaling pathways. These alternative pathways include additional signaling molecules, co-factors, and proteins to regulate various cellular responses to ER stress. These pathways, which can interact with components of the canonical UPR or act independently, are also crucial for maintaining cell homeostasis notably during plant-pathogen interactions.

### 6.1. The co-chaperone BAG7 takes part in UPR and immunity

One of the best-characterized non-canonical ER stress response
pathways is the BCL2-ASSOCIATED ATHANOGENE 7 (BAG7) that is associated with the bZIP28 signaling arm in *A. thaliana*. The BAG family is a widely conserved group of co-chaperones present in eukaryotes. The *Arabidopsis* genome contains seven homologs of the BAG family, each with a distinct subcellular localization. BAG7, a co-chaperone residing in the ER membrane, is essential for maintaining the UPR. On the lumen side, BAG7, bZIP28, and BiP interact in a protein complex, suggesting a potential involvement of BAG7 in retrograde ER-to-nucleus signaling (Fig. 2). It has been shown that BAG7 is involved in ER stress tolerance induced by heat stress. Its action depends on both its SUMOylation and its proteolytic cleavage, allowing its release from the membrane and its translocation into the nucleus where, it interacts with the WRKY29 TF [68,69]. Under non-stressed conditions, BAG7 is anchored in the ER membrane, retains bZIP28, and consequently inhibits ERSI. By contrast, treatment with culture filtrate of *Phytophthora capsici* triggers the release and translocation of BAG7 from the ER to the nucleus, where it activates ERSI and enhances resistance to this oomycete [69].

## 6.2. The susceptibility factor RTP1 participates in UPR

Another non-canonical UPR actor alongside bZIP28 is RTP1 (RESISTANCE TO PHYTOPHITHORA PARASITICA 1). This protein, located in the ER membrane, interacts with bZIP28 when transiently expressed in *N. benthamiana* leaves [56]. Moreover, RTP1 reduces the phosphorylation of IRE1B and its bZIP60 splicing activity. In *A. thaliana*, RTP1 have been shown to negatively regulate immunity against *P. parasitica* by restricting bZIP60 and bZIP28 signaling (Fig. 2). Interestingly, RTP1 also negatively regulates plant immunity against other biotrophic pathogens such as the bacterium *P. syringae* and the fungus *E. cichoracearum*, but not against the necrotrophic fungus *B. cinerea* [70]. Moreover, RTP1 regulates the expression of the *PR1* gene [70]. Altogether, these results suggest that RTP1 is a susceptibility factor that can play distinct roles depending on the pathogen's lifestyle.

## 6.3. The GTP-binding protein AGB1 participates in UPR and immunity

In plants, G proteins are involved in various developmental responses, phytohormone signaling, and plant immune responses [71]. G proteins are mainly associated with the plasma membrane, but the Arabidopsis GTP-Binding Protein β1-subunit (AGB1), has been detected at the ER membrane [72]. The *agb1* mutants are highly sensitive to ER stress, and the *ire1a ire1b agb1* triple mutant displays additive sensitivity [73,74]. Similarly, the Arabidopsis triple mutant also shows higher susceptibility against the virulent strain Pst DC3000 compared to *agb1* or *ire1a ire1b* double mutant (Fig. 2) [74]. These results suggest that IRE1 and AGB1 act non-redundantly and have a cumulative effect in ER stress signaling. Furthermore, under salt stress conditions, it has been demonstrated that AGB1 interacts with bZIP17 and contributes to the regulation of UPR genes [75]. Eventually, it is worth noting that in *A. thaliana*, the overexpression of *AGB1* reduces the bacterial leaf growth of Psm and *Pseudomonas syringae* pv. *tabaci*, in contrast to the knockout mutation that increases the growth of *P. syringae* pv. *phaseolicola* in leaves [76].

## 6.4. Many NAC transcription factors participate in ERSI

In addition to the UPR canonical signaling, other TFs are also involved in ERSI. The NAC (NAM/ATAF/CUC) which are recognized as one of the largest plant-specific TF families, contribute to the plant adaptation to many abiotic stresses and to developmental processes [77]. Some of them, called NTL (NAC with transmembrane motif1-like), possess a single transmembrane domain that served as anchor in the ER or plasma membrane [78]. Currently, five genes encoding NAC TFs (NAC017, NAC062, NAC089, NAC91, and NAC103) have been identified as involved in the UPR signaling in *A. thaliana* (Fig. 3). Under ER stress conditions, NAC017 (also called NTL7) is proteolytically cleaved and translocated from ER membrane to the nucleus to up-regulate

<figure><img src="image_6.png" /><figcaption>**Fig. 3.** Schematic representation of NAC (NAM/ATAF/CUC) transcription factors mediated unfolded protein response (UPR) pathways and their involvement during interactions with various pathogens. Endoplasmic reticulum (ER) stress induces the proteolytic release of membrane-associated NAC transcription factors, including NAC017, NAC062, NAC089 and NAC091. Once released, they translocate to the nucleus and regulate UPR, ER stress-mediated immunity (ERSI), or program cell death (PCD) related gene expression. NAC062 contributes to resistance against *P. syringae* pv. *tomato* DC3000 and *A. brassicicola*, but to susceptibility against *M. oryzae*. NAC089 enhances resistance to *P. capsici* and *P. syringae* pv. *tomato* DC3000. The yellow lightning symbol represents the induction of the UPR pathway in response to ER stress.</figcaption></figure>
pro-survival genes, including molecular chaperones and bZIP60 [79, 80]. Under ER stress conditions, NAC062 (also named NTL6) and NAC091 (also named Turnip Crinkle Virus interacting protein; TIP) are cleaved, releasing an active form that migrates from the plasma membrane to the nucleus, where it induces the activation of several UPR target genes. Among them, NAC062 regulates *BiP2*, *CNX1*, *CRT1* and *PDI5*, while NAC091 controls *ERdj3A*, *ERdj3B*, *BiP3*, *CRT1* and *bZIP28* [81,82]. The expression of NAC062 is directly regulated by bZIP60 [83] and the active form of NAC062 binds to the promoter of *NAC103*, inducing its expression and contributing to UPR gene activation [84]. While NAC062, NAC091 and NAC103 promote cell survival by inducing the expression of pro-adaptive UPR genes, NAC089 (also called NTL14) migrates from the ER to the nucleus to induce the expression of genes involved in PCD [81].

These NAC TFs can be involved in the transcriptional regulation of plant defense-related genes and thus play a role in ERSI (Fig. 3) [85]. For example, in *A. thaliana*, NAC062/NTL6 activates the transcription of *PR1*, *PR2* and *PR5* in cold conditions, improving resistance to *Pst* DC3000 [86]. In *O. sativa*, the ortholog of AtNAC062 negatively regulates the resistance against *Magnaporthe oryzae*, the causal agent of rice blast disease [87] and in *Brassica juncea*, NAC062/NTL6 improves resistance to *Alternaria brassicicola* [88]. In *A. thaliana*, NAC089 was identified as a crucial regulator of ERSI playing a key role in recognizing extracellular PAMPs during plant-pathogen interactions. For instance, it has been shown that NAC089/NTL14 increases resistance to *P. capsici* and *Pst* DC3000 in *A. thaliana* through the BAK1 receptor (BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1) [89].

Collectively, these data reveal that both non-canonical and canonical UPR actors contribute to plant immunity, functioning as either resistance or susceptibility factors, thereby supporting the pivotal role of

UPR signaling in plant-pathogen interactions.

## 7. The ER battlefield: pathogens target ER proteostasis

During the coevolution of plants and microbes, pathogens have evolved offensive strategies to efficiently parasitize their hosts. Pathogenic microbes secrete effectors that can hijack plant metabolism or defense systems, thereby facilitating their spread within the host. Recent studies have shown that ER is a target of many effectors with various mode of action. The first mechanism is directly related to the attenuation of ER stress by targeting the ER-QC machinery. In soybean plants infected by root and stem rots, the effector Avh262 is required for the full virulence of *Phytophthora sojae*. This effector targets BiPs and associates with them to increase their accumulation and stability. This lead to the restriction of bZIP28/BAG7 UPR arm, attenuation of ER stress, and finally the suppression of PCD, necessary to facilitate *P. sojae* development during its initial biotrophic phase of infection (Fig. 4 A) [69,90].

In *A. thaliana*, the *P. capsici* RXLR effector Avr3a12 interacts with the plant ER-localized peptidyl-prolyl cis-trans isomerase (PPIase) FKBP15-2 [91]. This PPIase catalyzes the trans-cis isomerization of prolyl residues, a process essential for proper protein folding [1]. Avr3a12 directly inhibits the FKBP15-2 activity that is essential for ERSI against *P. capsici*, thereby facilitating pathogen infection (Fig. 4B).

Targeting ER-QC chaperones with effectors is not a strategy exclusive to oomycete pathogens. BiP stabilization is also observed during the infection of a hybrid bamboo variety (*Bambusa pervariabilis* × *Dendrocalamopsis grandis*) by the fungus *Arthrinium phaeospermum*, inducing the branch wilting disease. More specifically, the effector cE12 interacts with ERdj to participate in BiP stabilization, likely enhancing UPR

<figure><img src="image_7.png" /><figcaption>**Fig. 4.** Effectors of various pathogens hijack the plant endoplasmic reticulum quality control (ER-QC) and unfolded protein response (UPR) pathways. (A) During the infection of *G. max*, *P. sojae* secretes the avirulence homolog effector PsAvh262 which induced stabilization and accumulation of the Binding immunoglobulin Protein (BiP) that blocked basic leucine zipper 28 and Bcl-2-associated athanogene 7 (bZIP28 / BAG7) signalization and thereby suppresses ER stress-induced cell death (PCD), promoting infection [69,90]. (B) During the infection of *A. thaliana*, *P. capsici* secretes the avirulence effector PcAvr3a12, which inhibits the host ER-localized peptidyl-prolyl cis-trans isomerase (PPIase) FKBP15-2, thereby dampening immunity [91]. (C) During the infection of bamboo (*Bambusa pervariabilis* × *Dendrocalamopsis grandis*), *A. phaseospermum* secretes the candidate effector ApcE12, which interacts with ER-localized DnaJ (ERdj), stabilizing BiP, thus enhancing UPR signalling, to suppress program cell death (PCD), and promote infection [92]. (D) During the infection of *H. vulgare*, *B. hordei* secretes the avirulence effector BhAVRA1 and the effector candidate BhBEC1016 which target ERdj3B, suppressing pathogen-associated molecular pattern-triggered immunity (PTI) [93].</figcaption></figure>
signaling and suppressing PCD, thereby facilitating infection [92] (Fig. 4 C).

Other chaperones have been shown to be targeted by effectors. The fungus *Blumeria hordei*, causing powdery mildew of barley (*Hordeum vulgare*), secretes hundreds of effectors. Two of them, $AVR_{A1}$ and BEC1016, target and interact with the ER-luminal protein ERdj3B, which is required for plant defense [93] (Fig. 4D). However, whether the biological activity of ERdj3B is regulated by $AVR_{A1}$ and BEC1016 remains unknown.

The sophisticated hijacking of major regulators of protein homeostasis within the ER raises the question of whether pathogens directly target ER stress regulators. This may represent a common mechanism of host manipulation, particularly in the case of filamentous microbes. By analyzing the sequences of effectors known to localize to the ER and secreted by *Hyaloperonospora arabidopsidi* and *Plasmopara halstedii* downy mildews agents in Arabidopsis and sunflower, respectively, Breeze et al. [94] identified a conserved C-terminal tail-anchor motif that is required for ER targeting. This motif has also been identified in several effectors secreted by *Phytophthora infestans*, the causal agent of potato late blight [94]. However, among the large number of predicted *P. infestans* effectors, those targeting the ER membrane represents only a small proportion [94]. Such effectors from various oomycetes can interact with NAC TFs, included NAC089 [94–96], indicating that this class of proteins is a key target for the host manipulation by various pathogens. The direct cellular or physiological impact of the interaction between effectors and NAC089 has not yet been elucidated. Furthermore, effectors targeting the ER may have a different mode of action from what has just been described. One such example is the *P. infestans* effector Avh262 that lacks a tail-anchor domain, but specifically targets the chaperone BiPs (Fig. 4 A) [90,94].

There is little data on whether molecules produced by necrotrophic fungi can interfere with the UPR pathway or other cellular pathways regulating ER stress. In *A. thaliana*, broad-spectrum necrotrophic fungus, *D. gigantea*, induces an extensive ER network destruction and vacuolization through the release of the toxin ophiobolin A (OP-A), triggering UPR activation, which is necessary for efficient defense [65]. One may postulate that extensive ER degradation and activation of ER stress led to widespread PCD, which is used by this kind of pathogen to support its colonization and growth.

In conclusion, hijacking of the ER-QC and the UPR by pathogens is a common mechanism and supports that ER proteostasis is one of the key players in plant immunity.

## 8. ER proteostasis on the battlefield: a double-edged sword

Like in all eukaryotic organisms, the ER-QC system and UPR signaling pathway are functionally conserved in phytopathogenic fungi and oomycetes, helping them to maintain ER proteostasis. In fungi, canonical UPR signaling is restricted to the IRE1 activity that can splice the mRNA of HAC1 (homolog of bZIP60) or participate in RIDD process [97]. During infection, pathogenic fungi produce numerous effectors that follow the anterograde pathway until being secreted. This mechanism, which is essential for infection, significantly increases the protein flux through the ER, leading to ER stress. Accordingly, maintaining ER proteostasis, through ER-QC and UPR, plays a pivotal role in pathogenesis [97] and was studied in different pathogens. In *M. oryzae*, the ER-resident chaperone LHS1 (LUMINAL HSP SEVENTY 1), which is involved in protein maturation and translocation across the ER membrane, also participates in UPR signaling [98]. The Δ*lhs1* deletion mutant severely reduces symptoms and induces lower expression of defense-related genes in rice leaves, supporting that ER-QC plays an important role in *M. oryzae* virulence. Similarly, under ER stress conditions, ERV29, a COPII (coated protein II) cargo receptor involved in transport from ER to Golgi apparatus, is upregulated by HAC1, promoting secretion from the ER to the Golgi apparatus [99]. The mutant Δ*erv29* causes limited lesion compared to WT *M. oryzae*. Finally, fungal

UPR is highly induced during infection [100] suggesting a link between ER proteostasis, vesicle trafficking and pathogenicity of *M. oryzae*.

Work on *B. cinerea* supports this hypothesis since the mutant Δ*sec13*, affected in the COPII outer shell component loses its pathogenicity [101]. Vesicle trafficking is also important for *B. cinerea* pathogenicity since a mutant impaired in clathrin heavy chain shows reduced necrotic lesions on bean leaves, cucumber cotyledons, and apple fruits [102]. The co-chaperone BAG1, which shares a relatively higher identity to AtBAG7, is involved in UPR signaling. The Δ*bag1* mutant shows growth inhibition under ER stress conditions triggered by heat and tunicamycin or dithiothreitol treatment [103]. Moreover, Δ*bag1* mutants can only trigger restricted lesions on tomato leaves and have low development on tomato fruit, suggesting that UPR is required for *B. cinerea* virulence.

Regarding *Ustilago maydis*, the causal agent of corn smut disease, the deletion mutants Δ*ire1* and Δ*cib1* (homolog of HAC1 and bZIP60) show attenuated symptoms associated with low penetration in maize leaves [104]. Likewise, the deletion mutant Δ*hac1* of *Colletotrichum fructicola* produces fewer conidia and fails to form appressoria and anthracnose symptoms on *Camellia oleifera* leaves [105]. In *A. brassicicola*, the deletion of *HacA* inhibits UPR signaling and restricts infection in *Brassica oleracea* and *A. thaliana* due to a decrease in protein (potentially effector) secretion capacity and cell wall defect [106], confirming the role of UPR in virulence of plant pathogen fungi.

These results exhibit a significant role of ER proteostasis during the pathogen infection process, thus allowing the host to counterattack by targeting the ER of pathogens. For example, in the plant defense arsenal, two phytoalexins, camalexin and brassinin, produced by *Brassicaceae* plants can activate UPR in the fungus *A. brassicicola*, [106,107]. Since the phytoalexin-deficient Arabidopsis mutant *pad3-1* exhibits higher susceptibility to *A. brassicicola* [108], one can assume that targeting the ER of pathogens contributes to plant defense. In the same way, it is worth noting that γ-mangostin 3, a natural prenylated polyhydroxyxanthone, can inhibit fungal IRE1 splicing activity, and thus reduce necrotic lesions induced by *A. brassicicola* and *B. cinerea* when applied on plants before infection [109]. Overall, these results allow us to propose a model in which ER proteostasis facilitate pathogen infection by enabling secretion of pathogenicity proteins (such as cutinases, proteases, or effectors), whereas plant ER proteostasis contributes to immunity through the production of defense proteins (like PR protein or PRR) within the so-called ERSI (Fig. 5). Following a coevolutionary dynamic, pathogens use effectors targeting ER proteostasis, and plants do the same through phytoalexin production.

## 9. Conclusion and perspectives

In recent years, research on cellular homeostasis, its maintenance, and the identification of key players involved in this process, particularly UPR and ER-QC, has gained significant attention within the plant-microbe-interaction scientific community. The UPR and the ER-QC are critical components enabling plants or fungi to maintain cellular homeostasis in response to environmental changes. Numerous progresses have been made in understanding the role of these processes in plant immunity, fungal pathogenicity, and the interplay between both interacting partners. This review highlights the crucial role of ER-QC, as ER chaperones are involved in plant immunity and targeted by pathogen effectors on the host side, and engaged in pathogenicity on the opposite side (Table S1). Likewise, the IRE1/bZIP60 arm of the UPR pathway is involved in both plant immunity and fungal pathogenicity, highlighting the importance of the canonical UPR signaling in plant-pathogen interactions (Table S1). This sheds light on the manipulation of ER proteostasis as a largely unexplored and emerging means for future improvement of crop resistance to pathogens. However, many studies were conducted on *A. thaliana*, and except for maize and rice, the UPR pathway is poorly characterized in crop species. Regarding the differences observed between plant species, such as the presence of one or two actors in the bZIP17/bZIP28 arm [40], further research is needed to
<figure><img src="image_8.png" /><figcaption>**Fig. 5.** Comparative model of the role the endoplasmic reticulum (ER) proteostasis during plant-cryptogamic interaction. In this model, the ER proteostasis of the pathogen plays a critical role in infection by participating in the folding and secretion of pathogenicity proteins. On the other side, plant endoplasmic reticulum quality control (ER-QC) and unfolded protein response (UPR) participates in immunity including ER stress-mediated immunity (ERSI)-related genes and secretion of defenses proteins. Given the importance of these mechanisms, pathogens effector hijack host ER proteostasis reducing immunity. In the same way, plants also target the ER of the pathogen through phytoalexin.</figcaption></figure>

uncover crop-specific variations and the intricate regulatory mechanisms that fine-tune the ERSI in the fields.

Elucidating these mechanisms may pave the way for innovative crop breeding strategies that boost disease resistance while reducing chemical reliance, contributing to sustainable agricultural systems. For this purpose, the role of ER-QC and UPR in biotic stress resistance, as well as the genetic variation of the germplasm for different crops, need to be thoroughly characterized. Moreover, studies on natural products targeting pathogens ER proteostasis must be further explored to characterize their impact on the ER of plants and fauna, thereby facilitating the development of new protection strategies based on disrupting pathogen ER proteostasis. In conclusion, targeting ER proteostasis in plants and pathogens offers a sustainable, innovative strategy to strengthen crop immunity and drive the agroecological transition.

## Funding

This work was supported by Université Bourgogne Europe for the funding for TM PhD (MESRI grant #2022-25) and EP PhD (MESRI grant #2025-28), the PIA4 HARMI excellence grant for EP, the FEDER UPR-ALGAE grant for OL, and ANER-Région Bourgogne Franche-Comté grant UPRInFoVigne for MG.

## Credit authorship contribution statement

TM, EP, OL and MG: Conceptualization and Writing - Original Draft. CB, NLC, BP, JLC, OL and MG: Writing - Review & Editing. All authors reviewed and approved the final version of the manuscript for publication.

## Declaration of Generative AI and AI-assisted technologies in the writing process

During the preparation of this work, the authors used OpenAI technologies in the writing process to improve the readability and language of the manuscript. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.

## Declaration of Competing Interest

The authors declare no conflicts of interest.

## Appendix A. Supporting information

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.cpb.2025.100552.

## Data availability

No data was used for the research described in the article.

## References

[1] I. Braakman, D.N. Hebert, Protein folding in the endoplasmic reticulum, a013201-a013201, Cold Spring Harb. Perspect. Biol. 5 (2013), https://doi.org/10.1101/cshperspect.a013201.

[2] S.H. Howell, Endoplasmic reticulum stress responses in plants, Annu. Rev. Plant Biol. 64 (2013) 477-499, https://doi.org/10.1146/annurev-arplant-050312-120053.

[3] R. Strasser, Protein quality control in the endoplasmic reticulum of plants, Annu. Rev. Plant Biol. 69 (2018) 147-172, https://doi.org/10.1146/annurev-arplant-042817-040331.
[4] P. Walter, D. Ron, The unfolded protein response: from stress pathway to homeostatic regulation, Science 334 (2011) 1081–1086, https://doi.org/10.1126/science.1209038.

[5] Y. Liu, J.S. Burgos, Y. Deng, R. Srivastava, S.H. Howell, D.C. Bassham, Degradation of the endoplasmic reticulum by autophagy during endoplasmic reticulum stress in arabidopsis, Plant Cell 24 (2012) 4635–4651, https://doi.org/10.1105/tpc.112.101535.

[6] D. Munch, E. Rodriguez, S. Bressendorff, O.K. Park, D. Hofius, M. Petersen, Autophagy deficiency leads to accumulation of ubiquitinated proteins, ER stress, and cell death in arabidopsis, Autophagy 10 (2014) 1579–1587, https://doi.org/10.4161/auto.29406.

[7] J.D.G. Jones, B.J. Staskawicz, J.L. Dangl, The plant immune system: from discovery to deployment, Cell 187 (2024) 2095–2116, https://doi.org/10.1016/j.cell.2024.03.045.

[8] M. Yuan, B.P.M. Ngou, P. Ding, X.-F. Xin, PTI-ETI crosstalk: an integrative view of plant immunity, Curr. Opin. Plant Biol. 62 (2021) 102030, https://doi.org/10.1016/j.pbi.2021.102030.

[9] T.A. DeFalco, C. Zipfel, Molecular mechanisms of early plant pattern-triggered immune signaling, Mol. Cell 81 (2021) 3449–3467, https://doi.org/10.1016/j.molcell.2021.07.029.

[10] J.D.G. Jones, J.L. Dangl, The plant immune system, Nature 444 (2006) 323–329, https://doi.org/10.1038/nature05286.

[11] Y. Wang, R.N. Pruitt, T. Nürnberger, Y. Wang, Evasion of plant immunity by microbial pathogens, Nat. Rev. Microbiol 20 (2022) 449–464, https://doi.org/10.1013/s41579-022-00710-3.

[12] P. Balint-Kurti, The plant hypersensitive response: concepts, control and consequences, Mol. Plant Pathol. 20 (2019) 1163–1178, https://doi.org/10.1111/mpp.12821.

[13] B.P.M. Ngou, P. Ding, J.D.G. Jones, Thirty years of resistance: Zig-zag through the plant immune system, Plant Cell 34 (2022) 1447–1478, https://doi.org/10.1093/plcell/koac041.

[14] B. Adhikari, J. Verchot, F. Brandizzi, D.K. Ko, ER stress and viral defense: advances and future perspectives on plant unfolded protein response in pathogenesis, J. Biol. Chem. 301 (2025) 108354, https://doi.org/10.1016/j.jbc.2025.108354.

[15] Y. Liu, S. Tian, T. Chen, Endoplasmic reticulum homeostasis in plant-pathogen interactions: new scenarios for an old story, J. Exp. Bot. 76 (2025) 277–284, https://doi.org/10.1093/jxb/erae404.

[16] I.S. Jeong, S. Lee, F. Bonkhofer, J. Tolley, A. Fukudome, Y. Nagashima, K. May, S. Rips, S.Y. Lee, P. Gallois, W.K. Russell, H.S. Jung, A. Von Schaewen, H. Koiwa, Purification and characterization of arabidopsis thaliana oligosaccharyltransferase complexes from the native host: a protein super-expression system for structural studies, Plant J. 94 (2018) 131–145, https://doi.org/10.1111/tpj.13847.

[17] D. Sung, F. Kaplan, C.L. Guy, Plant Hsp70 molecular chaperones: protein structure, gene family, expression and function, Physiol. Plant 113 (2001) 443–451, https://doi.org/10.1034/j.1399-3054.2001.1130402.x.

[18] V. Nekrasov, J. Li, M. Batoux, M. Roux, Z.-H. Chu, S. Lacombe, A. Rougon, P. Bittel, M. Kiss-Papp, D. Chinchilla, H.P. Van Esse, L. Jorda, B. Schwessinger, V. Nicaise, B.P.H.J. Thomma, A. Molina, J.D.G. Jones, C. Zipfel, Control of the pattern-recognition receptor EFR by an ER protein complex in plant immunity, EMBO J. 28 (2009) 3428–3438, https://doi.org/10.1038/emboj.2009.262.

[19] M.P. Ramirez, M. Rivera, D. Quiroga-Roger, A. Bustamante, M. Vega, M. Baez, E. M. Puchner, C.A.M. Wilson, Single molecule force spectroscopy reveals the effect of BiP chaperone on protein folding, Protein Sci. 26 (2017) 1404–1412, https://doi.org/10.1002/pro.3137.

[20] M. Ohta, Y. Wakasa, H. Takahashi, S. Hashi, K. Kudo, F. Takaiwa, Analysis of rice ER-resident J-proteins reveals diversity and functional differentiation of the ER-resident Hsp70 system in plants, J. Exp. Bot. 64 (2013) 5429–5441, https://doi.org/10.1093/jxb/ert312.

[21] R. Urade, Oxidative protein folding in the plant endoplasmic reticulum, Biosci. Biotechnol. Biochem 83 (2019) 781–793, https://doi.org/10.1080/09168451.2019.1571900.

[22] L. Wang, C. Wang, Oxidative protein folding fidelity and redoxosis in the endoplasmic reticulum, Trends Biochem. Sci. 48 (2023) 40–52, https://doi.org/10.1016/j.tibs.2022.06.011.

[23] Y. Nagashima, A. Von Schaewen, H. Koiwa, Function of N-glycosylation in plants, Plant Sci. 274 (2018) 70–79, https://doi.org/10.1016/j.plantsci.2018.05.007.

[24] J.-L. Sun, J.-Y. Li, M.-J. Wang, Z.-T. Song, J.-X. Liu, Protein quality control in plant organellae: current status and future perspectives, Mol. Plant 14 (2021) 95–114, https://doi.org/10.1016/j.molp.2020.10.011.

[25] C. Weis, S. Pfeilmeyer, E. Glawischning, E. Isono, F. Pachl, H. Hahne, B. Kuster, R. Eichmann, R. Hückelhoven, Co-immunoprecipitation-based identification of putative BAX INHIBITOR-1-interacting proteins involved in cell death regulation and plant-powdery mildew interactions, Mol. Plant Pathol. 14 (2013) 791–802, https://doi.org/10.1111/mpp.12050.

[26] L. Giordano, V. Allasia, A. Cremades, S. Hok, F. Panabières, B. Bailly-Maitre, H. Keller, A plant receptor domain with functional analogies to animal maleficent disables ER stress responses upon infection, iScience 25 (2022) 103877, https://doi.org/10.1016/j.isci.2022.103877.

[27] J. Li, C. Zhao-Hui, M. Batoux, V. Nekrasov, M. Roux, D. Chinchilla, C. Zipfel, J.D. G. Jones, Specific ER quality control components required for biogenesis of the plant innate immune receptor EFR, Proc. Natl. Acad. Sci. 106 (2009) 15973–15978, https://doi.org/10.1073/pnas.0905532106.

[28] L. Chen, S. Hamada, M. Fujiwara, T. Zhu, Y.H. Kim, N.P. Thao, H.L. Wong, P. Krishna, T. Ueda, H. Kaku, N. Shibuya, T. Kawasaki, K. Shimamoto, The Hop/Sti1-Hsp90 chaperone complex facilitates the maturation and transport of a

PAMP receptor in rice innate immunity, Cell Host Microbe 7 (2010) 185–196, https://doi.org/10.1016/j.chom.2010.02.008.

[29] D. Wang, N.D. Weaver, M. Kesarwani, X. Dong, Induction of protein secretory pathway is required for systemic acquired resistance, Science 308 (2005) 1036–1040, https://doi.org/10.1126/science.1108791.

[30] C. Blanchard, S. Aimé, A. Ducloy, S. Hichami, M. Azzopardi, J.-L. Cacas, O. Lamotte, The IRE1-bZIP60 branch of unfolded protein response is required for arabidopsis immune response to botrytis cinerea, J. Exp. Bot. (2025) eraf244, https://doi.org/10.1093/jxb/eraf244.

[31] H.H. Carvalho, P.A. Silva, G.C. Mendes, O.J.B. Brustolini, M.R. Pimenta, B. C. Gouveia, M.A.S. Valente, H.J.O. Ramos, J.R.L. Soares-Ramos, E.P.B. Fontes, The endoplasmic reticulum binding protein BiP displays dual function in modulating cell death events, Plant Physiol. 164 (2014) 654–670, https://doi.org/10.1104/pp.113.231928.

[32] J.M. Rodrigues, F.S. Coutinho, D.S. Dos Santos, C.E. Vital, J.R.L.S. Ramos, P. B. Reis, M.G.A. Oliveira, A. Mehta, E.P.B. Fontes, H.J.O. Ramos, BiP-overexpressing soybean plants display accelerated hypersensitivity response (HR) affecting the SA-dependent sphingolipid and flavonoid pathways, Phytochemistry 185 (2021) 112704, https://doi.org/10.1016/j.phytochem.2021.112704.

[33] G.D.M. Alcántara, G.C.B. Silva, I.Y.M. Ocampo, A.A. Kroger, R.S. De Oliveira, K. P. Gramacho, C.P. Pirovani, F.C. Alvim, Proteomic analysis of plants with binding immunoglobulin protein overexpression reveals mechanisms related to defense against moniliophthora perniciosa, Plants 14 (2025) 503, https://doi.org/10.3390/plants14040503.

[34] S. Ray, J.M. Anderson, F.I. Urmeev, S.B. Goodwin, Rapid induction of a protein disulfide isomerase and defense-related genes in wheat in response to the hemibiotrophic fungal pathogen mycosphaerella graminicola, Plant Mol. Biol. 53 (2003) 741–754, https://doi.org/10.1023/B:PLAN.0000019120.74610.52.

[35] T.W.H. Liebrand, P. Smit, A. Abd-El-Haliem, R. De Jonge, J.H.G. Cordewener, A. H.P. America, J. Sklenar, A.M.E. Jones, S. Robatzek, B.P.H.J. Thomma, W.I. L. Tameling, M.H.A.J. Joosten, Endoplasmic Reticulum-Quality control chaperones facilitate the biogenesis of Receptor-Like proteins involved in pathogen resistance of tomato, Plant Physiol. 159 (2012) 1819–1833, https://doi.org/10.1104/pp.112.196741.

[36] Y. Qiu, J. Xi, L. Du, S. Roje, B.W. Poovaiah, A dual regulatory role of arabidopsis calreticulin-2 in plant innate immunity, Plant J. 69 (2012) 489–500, https://doi.org/10.1111/j.1365-313X.2011.04807.x.

[37] M. Pröstbing, D. Schenke, R. Hossain, C. Häder, T. Thurau, L. Wighardt, A. Schuster, Z. Zhou, W. Ye, S. Rietz, G. Leckband, D. Cai, Loss of function of CRT1a (calreticulin) reduces plant susceptibility to verticillium longisporum in both arabidopsis thaliana and oilseed rape (brassica napus), Plant Biotechnol. J. 18 (2020) 2328–2344, https://doi.org/10.1111/pbi.13394.

[38] Q. Zhang, T. Sun, Y. Zhang, ER quality control components UGGT and STT3a are required for activation of defense responses in Bir1-1, PLOS ONE 10 (2015) e0120245, https://doi.org/10.1371/journal.pone.0120245.

[39] J. Hollien, Evolution of the unfolded protein response, Biochim. Biophys. Acta BBA Mol. Cell Res. 1833 (2013) 2458–2463, https://doi.org/10.1016/j.bbamcr.2013.01.016.

[40] S.H. Howell, Evolution of the unfolded protein response in plants, Plant Cell Environ. 44 (2021) 2625–2635, https://doi.org/10.1111/pec.14063.

[41] N. Koizumi, I.M. Martinez, Y. Kimata, K. Kohno, H. Sano, M.J. Chrispeels, Molecular characterization of two arabidopsis IRE1 homologs, endoplasmic Reticulum-Located transmembrane protein kinases, Plant Physiol. 127 (2001) 949–962, https://doi.org/10.1104/pp.010636.

[42] A. Bertolotti, Y. Zhang, L.M. Hendershot, H.P. Harding, D. Ron, Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response, Nat. Cell Biol. 2 (2000) 326–332, https://doi.org/10.1038/35014014.

[43] Y. Kimata, Y.I. Kimata, Y. Shimizu, H. Abe, I.C. Farcasanu, M. Takeuchi, M. D. Rose, K. Kohno, Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to accumulation of unfolded proteins, Mol. Biol. Cell 14 (2003) 2559–2569, https://doi.org/10.1091/mbc.e02-11-0708.

[44] B.M. Gardner, P. Walter, Unfolded proteins are Ire1-Activating ligands that directly induce the unfolded protein response, Science 333 (2011) 1891–1894, https://doi.org/10.1126/science.1209126.

[45] R. Carrillo, K. Iwai, A. Albertson, G. Dang, D.A. Christopher, Protein disulfide isomerase-9 interacts with the lumenal region of the transmembrane endoplasmic reticulum stress sensor kinase, IRE1, to modulate the unfolded protein response in arabidopsis, Front. Plant. Sci. 15 (2024) 1389658, https://doi.org/10.3389/fpls.2024.1389658.

[46] Y. Deng, S. Humbert, J.-X. Liu, R. Srivastava, S.J. Rothstein, S.H. Howell, Heat induces the splicing by IRE1 of a mRNA encoding a transcription factor involved in the unfolded protein response in arabidopsis, Proc. Natl. Acad. Sci. 108 (2011) 7247–7252, https://doi.org/10.1073/pnas.1102117108.

[47] K. Mishiba, Y. Iwata, T. Mochizuki, A. Matsumura, N. Nishioka, R. Hirata, N. Koizumi, Unfolded protein-independent IRE1 activation contributes to multifaceted developmental processes in arabidopsis, Life Sci. Alliance 2 (2019) e201900459, https://doi.org/10.26508/lsa.201900459.

[48] Y. Pu, C. Ruberti, E.R. Angelos, F. Brandizzi, AtIRE1C, an unconventional isoform of the UPR master regulator AtIRE1, is functionally associated with AtIRE1B in arabidopsis gametogenesis, Plant Direct 3 (2019) e00187, https://doi.org/10.1002/pld3.187.

[49] Y. Nagashima, K. Mishiba, E. Suzuki, Y. Shimada, Y. Iwata, N. Koizumi, Arabidopsis IRE1 catalyses unconventional splicing of bZIP60 mRNA to produce the active transcription factor, Sci. Rep. 1 (2011) 29, https://doi.org/10.1038/srep00029.
[50] K. Mishiba, Y. Nagashima, E. Suzuki, N. Hayashi, Y. Ogata, Y. Shimada, N. Koizumi, Defects in IRE1 enhance cell death and fail to degrade mRNAs encoding secretory pathway proteins in the *arabidopsis* unfolded protein response, Proc. Natl. Acad. Sci. 110 (2013) 5713–5718, https://doi.org/10.1073/pnas.121047110.

[51] Y. Bao, Y. Pu, X. Yu, B.D. Gregory, R. Srivastava, S.H. Howell, D.C. Bassham, IRE1B degrades RNAs encoding proteins that interfere with the induction of autophagy by ER stress in *arabidopsis thaliana*, Autophagy 14 (2018) 1562–1573, https://doi.org/10.1080/15548627.2018.1462426.

[52] R. Srivastava, Y. Deng, S. Shah, A.G. Rao, S.H. Howell, BINDING PROTEIN is a master regulator of the endoplasmic reticulum stress Sensor/Transducer bZIP28 in *arabidopsis*, Plant Cell 25 (2013) 1416–1429, https://doi.org/10.1105/tpc.113.110684.

[53] J.-X. Liu, R. Srivastava, P. Che, S.H. Howell, An endoplasmic reticulum stress response in *arabidopsis* is mediated by proteolytic processing and nuclear relocation of a Membrane-Associated transcription factor, bZIP28, Plant Cell 19 (2007) 4111–4119, https://doi.org/10.1105/tpc.106.050021.

[54] J.-X. Liu, R. Srivastava, P. Che, S.H. Howell, Salt stress responses in *arabidopsis* utilize a signal transduction pathway related to endoplasmic reticulum stress signaling: salt stress elicits ER stress response, Plant J. 51 (2007) 897–909, https://doi.org/10.1111/j.1365-313X.2007.03195.x.

[55] Y. Iwata, N. Koizumi, Unfolded protein response followed by induction of cell death in cultured tobacco cells treated with tunicamycin, Planta 220 (2005) 804–807, https://doi.org/10.1007/s00425-004-1479-z.

[56] X. Qiang, X. Liu, X. Wang, Q. Zheng, L. Kang, X. Gao, Y. Wei, W. Wu, W. Wu, H. Zhao, W. Shan, Susceptibility factor RTP1 negatively regulates phytophthora parasitica resistance via modulating UPR regulators bZIP60 and bZIP28, Plant Physiol. 186 (2021) 1269–1287, https://doi.org/10.1093/plphys/kiab126.

[57] Y.-H. Yu, Z.-L. Jiao, L. Bian, Y.-T. Wan, K.-K. Yu, G.-H. Zhang, D.-L. Guo, Overexpression of vitis vinifera VvZIP60 enhances Arabidopsis resistance to powdery mildew via the salicylic acid signaling pathway, Plant Sci. Hortic. 256 (2019) 108640, https://doi.org/10.1016/j.scienta.2019.108640.

[58] C. Tateda, R. Ozaki, Y. Onodera, Y. Takahashi, K. Yamaguchi, T. Berberich, N. Koizumi, T. Kusano, NtbZIP60, an endoplasmic reticulum-localized transcription factor, plays a role in the defense response against bacterial pathogens in nicotine tabacum, J. Plant Res. 121 (2008) 603–611, https://doi.org/10.1007/s10265-008-0185-5.

[59] Z. Xu, N. Song, L. Ma, J. Wu, IRE1-bZIP60 pathway is required for nicotiana attenuate resistance to fungal pathogen alternaria alternata, Front. Plant Sci. 10 (2019) 263, https://doi.org/10.3389/fpls.2019.00263.

[60] A.A. Moreno, M.S. Mukhtar, F. Blanco, J.L. Boatwright, I. Moreno, M.R. Jordan, Y. Chen, F. Brandizzi, X. Dong, A. Orellana, K.M. Pajerowska-Mukhtar, IRE1/bZIP60-Mediated unfolded protein response plays distinct roles in plant immunity and abiotic stress responses, PLoS ONE 7 (2012) e31944, https://doi.org/10.1371/journal.pone.0031944.

[61] R. Chakraborty, S. Uddin, D.M. Macoy, S.O. Park, D.T. Van Anh, G.R. Ryu, Y. H. Kim, J.-Y. Lee, J.-Y. Cha, W.-Y. Kim, S.Y. Lee, M.G. Kim, Inositol-requiring enzyme 1 (IRE1) plays for AvrRpt2-triggered immunity and RIN4 cleavage in arabidopsis under endoplasmic reticulum (ER) stress, Plant Physiol. Biochem 156 (2020) 105–114, https://doi.org/10.1016/j.plaphy.2020.09.002.

[62] C. Liu, D. Hao, R. Sun, Y. Zhang, Y. Peng, Y. Yuan, K. Jiang, W. Li, X. Wen, H. Guo, Arabidopsis NPF2.13 functions as a critical transporter of bacterial natural compound tunicamycin in plant-microbe interaction, N. Phytol. 238 (2023) 765–780, https://doi.org/10.1111/nph.18752.

[63] A. Ducloy, M. Azzopardi, C. Ivsic, G. Gueff, D. Sourdeval, D. Charif, J.-L. Cacas, A transcriptomic dataset for investigating the Arabidopsis unfolded protein response under chronic, proteotoxic endoplasmic reticulum stress, Data Brief. 53 (2024) 110243, https://doi.org/10.1016/j.dib.2024.110243.

[64] P. Arraia-Salinas, J. Domínguez-Figueroa, A. Herrera-Vásquez, D. Zavala, J. Medina, J. Vicente-Carbajosa, C. Meneses, P. Canessa, R. Campos-Vargas, A. A. Moreno, F. Blanco-Herrera, WRKY7, -11 and -17 transcription factors are modulators of the bZIP28 branch of the unfolded protein response during PAMP-triggered immunity in *arabidopsis thaliana*, Plant Sci. 277 (2018) 242–250, https://doi.org/10.1016/j.plantsci.2018.09.019.

[65] S. Samperna, A. Boari, M. Vurro, A.M. Salzano, P. Reveglia, A. Evidente, A. Gismondi, A. Canini, A. Caloni, M. Marra, Arabidopsis defense against the pathogenic fungus drechslera gigantea is dependent on the integrity of the unfolded protein response, Biomolecules 11 (2021) 240, https://doi.org/10.3390/biom11020240.

[66] M. Nakamura, M. Nozaki, Y. Iwata, N. Koizumi, Y. Sato, THESEUS1 is involved in tunicamycin-induced root growth inhibition, ectopic lignin deposition, and cell wall damage-induced unfolded protein response, Plant Biotechnol. 39 (2022) 129–138, https://doi.org/10.5511/plantbiotechnology.21.1224a.

[67] M. Lee, H.S. Jeon, S.H. Kim, J.H. Chung, D. Roppolo, H. Lee, H.J. Cho, Y. Tobimatsu, J. Ralph, O.K. Park, Lignin-based barrier restricts pathogens to the infection site and confers resistance in plants, EMBO J. 38 (2019) e101948, https://doi.org/10.15252/embj.201901948.

[68] Y. Li, B. Williams, M. Dickman, Arabidopsis B-cell lymphoma2 (Bcl-2)-associated athanogene 7 (BAG 7)-mediated heat tolerance requires translocation, sumoylation and binding to WRKY 29, N. Phytol. 214 (2017) 695–705, https://doi.org/10.1111/nph.14388.

[69] Y. Zhou, K. Yang, M. Cheng, Y. Cheng, Y. Li, G. Ai, T. Bai, R. Xu, W. Duan, H. Peng, X. Li, A. Xia, Y. Wang, M. Jing, D. Dou, M.B. Dickman, Double-faced role of Bcl-2-associated athanogene 7 in plant- *phytophthora* interaction, J. Exp. Bot. 72 (2021) 5751–5765, https://doi.org/10.1093/jxb/erab252.

[70] Q. Pan, B. Cui, F. Deng, J. Quan, G.J. Loake, W. Shan, N. Phytol. 209 (2016) 1641–1654, https://doi.org/10.1111/nph.13707.

[71] S. Pandey, Heterotrimeric G-Protein signaling in plants: conserved and novel mechanisms, Annu. Rev. Plant Biol. 70 (2019) 213–238, https://doi.org/10.1146/annurev-applant-050718-100231.

[72] S. Wang, S. Narendra, N. Fedoroff, Heterotrimeric g protein signaling in the *arabidopsis* unfolded protein response, Proc. Natl. Acad. Sci. 104 (2007) 3817–3822, https://doi.org/10.1073/pnas.0611735104.

[73] Y. Chen, F. Brandizzi, AtIRE1A/AtIRE1B and AGB1 independently control two essential unfolded protein response pathways in arabidopsis, Plant J. 69 (2012) 266–277, https://doi.org/10.1111/j.1365-313X.2011.04788.x.

[74] T. Afrin, C.N. Costello, A.N. Monella, C.J. Körner, K.M. Pajerowska-Mukhtar, The interplay of GTP-binding protein AGB1 with ER stress sensors IRE1a and IRE1b modulates arabidopsis unfolded protein response and bacterial immunity, Plant Signal. Behav. 17 (2022) 2018857, https://doi.org/10.1080/15592324.2021.2018857.

[75] Y. Cho, Arabidopsis AGB1 participates in salinity response through bZIP17-mediated unfolded protein response, BMC Plant Biol. 24 (2024), https://doi.org/10.1186/s12870-024-05296-x.

[76] S. Lee, C.M. Rojas, Y. Ishiga, S. Pandey, K.S. Mysore, Arabidopsis heterotrimeric G-Proteins play a critical role in host and nonhost resistance against pseudomonas syringae pathogens, PLoS ONE 8 (2013) e82445, https://doi.org/10.1371/journal.pone.0082445.

[77] H. Xiong, H. He, Y. Chang, B. Miao, Z. Liu, Q. Wang, F. Dong, L. Xiong, Multiple roles of NAC transcription factors in plant development and stress responses, J. Integr. Plant Biol. 67 (2025) 510–538, https://doi.org/10.1111/jipb.13854.

[78] L. Shu, L. Li, Y.-Q. Jiang, J. Yan, Advances in membrane-tethered NAC transcription factors in plants, Plant Sci. 342 (2024) 112034, https://doi.org/10.1016/j.plantsci.2024.112034.

[79] S. Ng, A. Ivanova, O. Duncan, S.R. Law, O. Van Aken, I. De Clercq, Y. Wang, C. Carrie, L. Xu, B. Kmiec, H. Walker, F. Van Breusegem, J. Whelan, E. Giraud, A Membrane-Bound NAC transcription factor, ANAC017, mediates mitochondrial retrograde signaling in *arabidopsis*, Plant Cell 25 (2013) 3450–3471, https://doi.org/10.1105/tpc.113.113985.

[80] Y.H. Chi, S.M.B. Melencion, C.V. Alinapon, M.J. Kim, E.S. Lee, S.K. Paeng, J. H. Park, G.M. Nawkar, Y.J. Jung, H.B. Chae, C.H. Kang, S.Y. Lee, The membrane-tethered NAC transcription factor, AtNTL7, contributes to ER-stress resistance in arabidopsis, Biochem. Biophys. Res. Commun. 488 (2017) 641–647, https://doi.org/10.1016/j.bbcrc.2017.01.047.

[81] Z. Yang, S. Lu, M. Wang, D. Bi, L. Sun, S. Zhou, Z. Song, J. Liu, A plasma membrane-tethered transcription factor, NAC 062/ ANAC 062/ NTL 6, mediates the unfolded protein response in arabidopsis, Plant J. 79 (2014) 1033–1043, https://doi.org/10.1111/tpj.12604.

[82] Z.-T. Yang, S.-X. Fan, J.-J. Wang, Y. An, Z.-Q. Guo, K. Li, J.-X. Liu, The plasma membrane-associated transcription factor NAC091 regulates unfolded protein response in arabidopsis thaliana, Plant Sci. 334 (2023) 111777, https://doi.org/10.1016/j.plantsci.2023.111777.

[83] Z.-T. Yang, M.-J. Wang, L. Sun, S.-J. Lu, D.-L. Bi, L. Sun, Z.-T. Song, S.-S. Zhang, S.-F. Zhou, J.-X. Liu, The Membrane-Associated transcription factor NAC089 controls ER-Stress-Induced programmed cell death in plants, PLoS Genet 10 (2014) e1004243, https://doi.org/10.1371/journal.pgen.1004243.

[84] Z. Yang, Z. Guo, S. Wang, Y. An, S. Fan, Y. Jian, K. Li, Y. Yi, NAC062 acts as an upstream regulator of *nac103* under endoplasmic reticulum stress, Agron. J. 114 (2022) 191–194, https://doi.org/10.1002/agj2.20975.

[85] D.W.-K. Ng, J.K. Abeyasinghe, M. Kamali, Regulating the regulators: the control of transcription factors in plant defense signaling, Int. J. Mol. Sci. 19 (2018) 3737, https://doi.org/10.3390/ijms19123737.

[86] P.J. Seo, M.J. Kim, J.-Y. Park, S.-Y. Kim, J. Jeon, Y.-H. Lee, J. Kim, C.-M. Park, Cold activation of a plasma membrane-tethered NAC transcription factor induces a pathogen resistance response in arabidopsis, Plant J. 61 (2010) 661–671, https://doi.org/10.1111/j.1365-313X.2009.04091.x.

[87] F. Meng, Q. Zhao, X. Zhao, C. Yang, R. Liu, J. Pang, W. Zhao, Q. Wang, M. Liu, Z. Zhang, Z. Kong, J. Liu, A rice protein modulates endoplasmic reticulum homeostasis and coordinates with a transcription factor to initiate blast disease resistance, Cell Rep. 39 (2022) 110941, https://doi.org/10.1016/j.celrep.2022.110941.

[88] B. Mondal, A. Mukherjee, M. Mazumder, A. De, S. Ghosh, D. Basu, Inducible expression of truncated NAC62 provides tolerance against alternaria brassicicola and imparts developmental changes in Indian mustard, Plant Sci. 324 (2022) 111425, https://doi.org/10.1016/j.plantsci.2022.111425.

[89] G. Ai, H. Zhu, X. Fu, J. Liu, T. Li, Y. Cheng, Y. Zhang, K. Yang, W. Pan, H. Zhang, Z. Wu, S. Dong, Y. Xia, Y. Wang, A. Xia, Y. Wang, D. Dou, M. Jing, *phytophthora* infection signals-induced translocation of NAC089 is required for endoplasmic reticulum stress response-mediated plant immunity, Plant J. 108 (2021) 67–80, https://doi.org/10.1111/tpj.15425.

[90] M. Jing, B. Guo, H. Li, B. Yang, H. Wang, G. Kong, Y. Zhao, H. Xu, Y. Wang, W. Ye, S. Dong, Y. Qiao, B.M. Tyler, W. Ma, Y. Wang, A phytophthora sojae effector suppresses endoplasmic reticulum stress-mediated immunity by stabilizing plant binding immunoglobulin proteins, Nat. Commun. 7 (2016) 11685, https://doi.org/10.1038/ncomms11685.

[91] G. Fan, Y. Yang, T. Li, W. Lu, Y. Du, X. Qiang, Q. Wen, W. Shan, A phytophthora capsici RXLR effector targets and inhibits a plant PPIase to suppress endoplasmic Reticulum-Mediated immunity, Mol. Plant 11 (2018) 1067–1083, https://doi.org/10.1016/j.molp.2018.05.009.

[92] F. Luo, X. Fang, H. Luo, Z. Ye, S. Liu, H. Zhao, S. Li, S. Li, Targeting of the hybrid bamboo BDDNAJ by pathogen effector APCe12 regulates the unfolded protein
response, Mol. Plant Pathol. 26 (2025) e70089, https://doi.org/10.1111/
mpp.70089.

[93] Z. Li, V. Velásquez-Zapata, J.M. Elmore, X. Li, W. Xie, S. Deb, X. Tian, S. Banerjee, H.J.L. Jørgensen, C. Pedersen, R.P. Wise, H. Thordal-Christensen, Powdery mildew effectors *ARV<sub>A1</sub>* and *BEC1016* target the ER J-domain protein *hv ERdj3B* required for immunity in barley, Mol. Plant Pathol. 25 (2024) e13463, https://doi.org/10.1111/mpp.13463.

[94] E. Breeze, V. Vale, H. McLellan, Y. Pecrix, L. Godiard, M. Grant, L. Frigerio, A tell tail sign: a conserved C-terminal tail-anchor domain targets a subset of pathogen effectors to the plant endoplasmic reticulum, J. Exp. Bot. 74 (2023) 3188–3202, https://doi.org/10.1093/jxb/erad075.

[95] M.S. Mukhtar, A.-R. Carvunis, M. Drezé, P. Epple, J. Steinbrenner, J. Moore, M. Tasan, M. Galli, T. Hao, M.T. Nishimura, S.J. Pevzner, S.E. Donovan, L. Ghamsari, B. Santhanam, V. Romero, M.M. Poulin, F. Gebreab, B.J. Gutierrez, S. Tam, D. Monachello, M. Boxem, C.J. Harbort, N. McDonald, L. Gai, H. Chen, Y. He, European Union Effectoromics Consortium, J. Vandenhaute, F.P. Roth, D. E. Hill, J.R. Ecker, M. Vidal, J. Beynon, P. Braun, J.L. Dangl, Independently evolved virulence effectors converge onto hubs in a plant immune system network, Science 333 (2011) 596–601, https://doi.org/10.1126/
science.1203659.

[96] C. Meisrimler, A.J.E. Pelgrom, B. Oud, S. Out, G. Van Den Ackerveken, Multiple downy mildew effectors target the stress-related NAC transcription factor is NAC 069 in lettuce, Plant J. 99 (2019) 1098–1115, https://doi.org/10.1111/
tpj.14383.

[97] K. Krishnan, D.S. Askew, Endoplasmic reticulum stress and fungal pathogenesis, Fungal Biol. Rev. 28 (2014) 29–35, https://doi.org/10.1016/j.fbr.2014.07.001.

[98] M. Yi, M.-H. Chi, C.H. Khang, S.-Y. Park, S. Kang, B. Valent, Y.-H. Lee, The ER chaperone LHS1 is involved in asexual development and rice infection by the blast fungus *magnaporthe oryzae*, Plant Cell 21 (2009) 681–695, https://doi.org/
10.1105/tpc.107.055988.

[99] B. Qian, X. Su, Z. Ye, X. Liu, M. Liu, D. Shen, H. Chen, H. Zhang, P. Wang, Z. Zhang, MoErv29 promotes apoplastic effector secretion contributing to virulence of the rice blast fungus *magnaporthe oryzae*, N. Phytol. 233 (2022) 1289–1302, https://doi.org/10.1111/nph.17851.

[100] Z. Yin, W. Feng, C. Chen, J. Xu, Y. Li, L. Yang, J. Wang, X. Liu, W. Wang, C. Gao, H. Zhang, X. Zheng, P. Wang, Z. Zhang, Shedding light on autophagy coordinating with cell wall integrity signaling to govern pathogenicity of *magnaporthe oryzae*, Autophagy 16 (2020) 900–916, https://doi.org/10.1080/
15548627.2019.1644075.

[101] H. Qian, M.-H. Wu, W.-H. Zhao, X.-M. Zhu, L.-X. Sun, J.-P. Lu, D.J. Klionsky, F.-C. Lin, X.-H. Liu, MoSec13 combined with MoGcn5b modulates MoAtg8 acetylation and regulates autophagy in *magnaporthe oryzae*, Autophagy (2025) 1–18, https://doi.org/10.1080/15548627.2025.2499289.

[102] E. Souibgui, C. Bruel, M. Choquer, A. De Vallée, C. Dieryckx, J.W. Dupuy, M.-P. Latorse, C. Rascle, N. Poussereau, Clathrin is important for virulence factors delivery in the necrotrophic fungus botrytis cinerea, Front. Plant Sci. 12 (2021) 668937, https://doi.org/10.3389/fpls.2021.668937.

[103] H. Zhang, Y. Li, M.B. Dickman, Z. Wang, Cytoprotective Co-chaperone BcBAG1 is a component for fungal development, virulence, and unfolded protein response (UPR) of botrytis cinerea, Front. Microbiol 10 (2019) 685, https://doi.org/
10.3389/fmicb.2019.00685.

[104] K. Heimel, J. Freitag, M. Hampel, J. Ast, M. Bölker, J. Kämper, Crosstalk between the unfolded protein response and pathways that regulate pathogenic development in *ustilago maydis*, Plant Cell 25 (2013) 4262–4277, https://doi.org/
10.1105/tpc.113.115899.

[105] S. Li, Y. Guo, S. Zhang, H. Li, The transcription factor CfHac1 regulates the degradation of ubiquitin-mediated ER-associated misfolded proteins and pathogenicity in colletotrichum fructicola, Stress Biol. 5 (2025), https://doi.org/
10.1007/s44154-025-00237-6.

[106] A. Joubert, P. Simoneau, C. Campion, N. Bataillé-Simoneau, B. Iacomi-Vasilescu, P. Poupard, J.M. Francois, S. Georgault, E. Sellier, T. Guillemette, Impact of the unfolded protein response on the pathogenicity of the necrotrophic fungus *alternaria brassicicola*, Mol. Microbiol 79 (2011) 1305–1324, https://doi.org/
10.1111/j.1365-2958.2010.07522.x.

[107] G.Q. N'Guyen, R. Raulo, A. Porquier, B. Iacomi, S. Pelletier, J.-P. Renou, N. Bataillé-Simoneau, C. Campion, B. Hamon, A. Kwasiborski, J. Colou, A. Benamar, P. Hudhomme, D. Macherel, P. Simoneau, T. Guillemette, Responses of the necrotrophic fungus *alternaria brassicicola* to the indolic phytoalexin brassinin, Front. Plant Sci. 11 (2021) 611643, https://doi.org/10.3389/
fpls.2020.611643.

[108] B.P.H.J. Thomma, I. Nelissen, K. Eggermont, W.F. Broekaert, Deficiency in phytoalexin production causes enhanced susceptibility of arabidopsis thaliana to the fungus *alternaria brassicicola*, Plant J. 19 (1999) 163–171, https://doi.org/
10.1046/j.1365-313X.1999.00513.x.

[109] T. Charpentier, G. Viault, A.-M. Le Ray, N. Bataillé-Simoneau, J.-J. Helesbeux, N. Blon, F. Bastide, M. Marchi, S. Aligon, A. Bruguière, C.P. Dinh, Z. Benbelkacem, J.-F. Dallery, P. Simoneau, P. Richomme, T. Guillemette, Natural products targeting the fungal unfolded protein response as an alternative crop

protection strategy, J. Agric. Food Chem. 71 (2023) 13706–13716, https://doi.
org/10.1021/acs.jafc.3c03602.

Glossary

AGB1: Arabidopsis GTP-Binding Protein β1-subunit

ATP: Adenosine Triphosphate

Avr: Avirulence effector

BAG7: BCL2-ASSOCIATED ATHANOGENE 7

BAK1: BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1

BIP: Binding Immunoglobulin Protein

bZIP: Basic Leucine Zipper

bZIP60s: Spliced bZIP60

bZIP60u: Unspliced bZIP60

CNX: Calnexin

COPII: Coated Protein II

CRT: Calreticulin

DAMPs: Damage-Associated Molecular Patterns

DNA: Deoxyribonucleic Acid

EDS1: ENHANCED DISEASE SUSCEPTIBILITY 1

EFR: EF-Tu receptor

ER: Endoplasmic Reticulum

ERAD: ER-Associated Degradation

ERdj3: ER-Localized Dnaj-3

ERO1: ER OXIDOREDUCTASE-1

ER-QC: ER Quality Control

ERSI: ER Stress-Mediated Immunity

ETI: Effector-Triggered Immunity

ETS: Effector-Triggered Susceptibility

FLS2: Flagellin Sensing 2 Receptor

GCSI: Glucosidases I

GCSII: Glucosidases II

Glc: Glucose

HAP6: ER-Residing Ribophorin HAPLESS 6

HR: Hypersensitive Response

Hsp70: Heat Shock Protein 70

IRE1: Inositol Requiring Enzyme 1

JA: Jasmonic Acid

LHS1: LUMINAL HSP SEVENTY 1

LRR-RLK: Leucine-Rich Repeat- Receptor-Like Kinase

MAMPs: Microbial-Associated Molecular Patterns

MAPK: Mitogen-Activated Protein Kinase

MLO4: Mildew Resistance Locus 4

MNS: α-mannosidase enzymes

N: Asparaginyl

NBD: Nucleotide-Binding Domain

NLRs: Nucleotide-Binding Domain Leucine-Rich Repeat Containing Receptors

NTL: NAC With Transmembrane Motif1-Like

OP-A: Toxin Ophiobolin A

OST: Oligosaccharyltransferase

PAMPs: Pathogen-Associated Molecular Patterns

PCD: Programmed Cell Death

PDI: Protein Disulfide Isomerase

PPIase: Peptidyl-Prolyl Cis-Trans Isomerase

PR: Pathogenesis-Related

PRRs: Pattern Recognition Receptors

Psm: Pseudomonas syringae pv. maculicola

Pst: Pseudomonas syringae pv. tomato

PTI: Pattern-Triggered Immunity

RIDD: Regulated Ire1-Dependent Decay

RNA: Ribonucleic Acid

ROS: Reactive Oxygen Species

RPN2: RIBOPHORIN II

RTPI: RESISTANCE TO PHYTOPHITHORA PARASITICA 1

S1P: Resident Site-1 Proteases

S2P: Resident Site-2 Proteases

SA: Salicylic Acid

SBD: Substrate Binding Domain

SDF2: STROMAL CELL-DERIVED FACTOR 2

SOBIR1: SUPPRESSOR OF BIR1-1

TFs: Transcription Factors

TIP: Turnip Crinkle Virus Interacting Protein

UGGT: UDP-Glucose Glycoprotein Glucosyltransferase

UPR: Unfolded Protein Response

WT: Wild Type