## 4 Discussion
### DaMDHAR-Dependent PM Stabilization at the mRNA Level against FT  
PM is frequently challenged to abiotic stresses. To minimize stress-mediated PM damage, aerobic cells have a broad range of defense systems. Considering these facts, _DaMDHAR_-dependent cell rescue systems on PM were explored under FT2 stress. In relation to PM, _DaMDHAR_-expressing DM cells upregulated a wide range of genes under FT2 stress compared with WT cells, but they downregulated _ZEO1_, _MAL31_, _RIM9_, _MPH2_, _HXT3_, _SMA1_, _HXT17_, and _HSP30_ under the same conditions (Figures 3-5 and Figure 7A; Tables 1 and 2 and Tables S2-S6). In yeast, several sensing systems localized to PM regulate the expression and activity of a protein involved in nutrient uptake and metabolism [108]. For instance, gene activation encoding various nutrient permeases, including the ammonium permease Mep1, methionine permease Mup1, and general amino acid permease Gap1, regulates nutrient homeostasis and cyclic AMP-mediated fast energy recycling to overcome environmental stress such as FT [109].  
Overexpressed _PUT4_ encoding specific proline permease facilitates stress resistance to heat shock and osmolarity via proline uptake [110]. _UGA4_ encoding \(\gamma\)-aminobutyric acid and \(\delta\)-aminolevulinic acid permease are regulated by extracellular amino acids condition [108]. Uregulated _ATO3_ encoding a putative PM ammonium transporter is associated with eliminating the excess ammonia produced during amino acid metabolism via the outward ammonia release [111]. By contrast, downregulated _RIM9_ is considered an auxiliary component of the pH sensor machinery upon external alkalization [112]. The downregulation or deletion of _HSP30_ abolished the pH buffering activity instead of shifting cytosolic pH [87]. High change expression of these genes may rapidly regulate the cellular nutrients and pH homeostasis between the PM and other organs _SIP18_ with PM phospholipid-binding hydrophilic activity wad upregulated in DM cells under FT2 stress, whereas _YNLI90W_ with cell wall hydrophilic activity was downregulated under the same condition (Tables 1 and 2). _SIP18_-dependent genetic improvement prevented cell death during desiccation and freezing stress [113; 114; 115]. In addition, upregulated _HSP12_ belonging to the hydrophilic family can reinforce stress tolerance by preventing severe water loss under desiccation stress [116]. By contrast, _YNLI90W_ downregulated in DM cells is induced in response to organic solvents [117; 118]. The expression combination of SIP18_ and _HSP12_ genes could maximize rehydration from environmental stress causing water loss such as FT2 stress. By contrast, highly accumulated _PDR15_ and _YKR104W_ expression encoding a multidrug-resistant protein enhance stress resistance to intracellular xenobiotics produced during FT2 stress, and their inactivation increase xenobiotic sensitivity [119; 120]. _DaMDHAR_ expression confers stress tolerance by preventing dehydration and detoxifying toxic xenobiotics triggered during FT2 stress. Thus, these results indicate that the maintenance of PM integrity after physical damage is critical for FT stress response; retaining proper membrane function and flexibility increases cell survival by allowing more efficient dehydration.