## 5 Conclusions  
The mechanisms behind FT stress response have not been fully elucidated in yeast, particularly those related to the ways in which different signals are integrated to regulate tolerance responses. We investigated the relationship between response and tolerance mechanism in transgenic yeast expressing _DaMDHAR_. _DaMDHAR_-dependent tolerance was mediated by the rapid, effective gene expression program related to the detoxification of ROS, prevention of water loss, import of amino acids, sugar, phosphate, and iron, the export of toxic ammonia, proton, and xenobiotics, activation of PPP and methionine metabolism, sulfur assimilation, and glycogen synthesis during FT2 stress. As a result, _DaMDHAR_-transgenic yeast cells could maintain a broad range of homeostasis of redox state, ion, phosphate, amino acids, water and sugar, as well as an NADPH pool. In addition, the state of desiccation and oxidative stress is linked with the reversible delay of metabolism due to the FT of cells. The functionality and metabolism of mitochondria and stabilization via the altered structure or composition of PM and cell wall are associated with parameters strongly affecting yeast cell stress resistance during FT exposure and damage to organelles, including mitochondria, PM, and cell wall during FT2 stress can be a key component causing stress sensitivity (Figure 9). In the future, the functionality of unknown genes on cellular stress response needs to be elucidated as various genes encoding the hypothetical protein occupy more than 40% of the identified genes.  
Figure 9: Summary diagram of the adaptive molecular mechanism involved in FT2 stress response in _DaMDHAR_-expressing yeast cells.  
**Supplementary Materials:** The following are available online at [[https://www.mdpi.com/2073-4](https://www.mdpi.com/2073-4)]([https://www.mdpi.com/2073-4](https://www.mdpi.com/2073-4)) 425/12/2/219/s1, Table S1: Genotype of _S. cerevisiae_ strains used in this study, Table S2: Twofold changed genes in _DaMDHAR_-expressing yeast cells to FT stress, Table S3: GO-based classification of upregulated genes in _DaMDHAR_-expressing yeast cells; Table S4: Kyoto Encyclopedia of Genes and Genomes (KEGG)-based classification of upregulated genes in _DaMDHAR_-expressing yeast cells, Table S5: GO-based classification of downregulated genes in _DaMDHAR_-expressing yeast cells, Table S6: KEGG-based classification of downregulated genes in _DaMDHAR_-expressing yeast cells.  
**Author Contributions:** Conceptualization, H.-W.K. and I.-S.K.; methodology, W.C. and I.-S.K.; software, J.S. and I.-S.K.; validation, S.C.S., H.-W.K. and I.-S.K.; formal analysis, S.C.S., J.H.L. and I.-S.K.; investigation, H.-W.K.; resources, H.L., J.L. and H.-W.K.; data curation, W.C., H.-W.K. and I.-S.K.; writing--original draft preparation, H.-W.K. and I.-S.K.; writing--review and editing, H.-W.K. and I.-S.K.; visualization, I.-S.K.; supervision, H.-W.K. and I.-S.K.; project administration, H.-W.K. and I.-S.K.; funding acquisition, J.H.L., H.-W.K. and I.-S.K. All authors have read and agreed to the published version of the manuscript.  
**Funding:** This study was supported by grants from the National Research Foundation of Korea (NRF-2019R1 IIA1A01058109) and the Korea Polar Research Institute (KOPRI; grant numbers PE21160). This research was also a part of the project titled \"Development of potential antibiotic compounds using polar organism resources (15250103, KOPRI Grant PM20030)\", funded by the Ministry of Oceans and Fisheries, Korea and National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1G1A1100765).  
**Institutional Review Board Statement:** Not applicable.  
**Informed Consent Statement:** Not applicable.  
**Conflicts of Interest:** The authors declare no conflict of interest.