The ethanol tolerance in Saccharomyces cerevisiae under a phenomics perspective

Ethanol (EtOH) is a substantial stressor for Saccharomyces cerevisiae . Data integration from strains with different phenotypes, including EtOH stress-responsive lncRNAs, are still not available. We covered these issues seeking systems modifications that drive the divergences between higher (HT) and lower (LT) EtOH tolerant strains under their highest stress conditions. We showed that these phenotypes are neither related to high viability nor faster population rebound after stress relief. LncRNAs work on many stress-responsive systems in a strain-specific manner promoting the EtOH tolerance. Cells use membraneless RNA/protein storage and degradation systems to endure the stress harming, and lncRNAs jointly promote EtOH tolerance. CTA1 and longevity are primer systems promoting phenotype-specific gene expression. The lower cell viability and growth under stress is a byproduct of sphingolipids and inositol phosphorylceramide dampening, acerbated in HTs by sphinganine, ERG9, and squalene overloads; LTs diminish this harm by accumulating inositol 1-phosphate. The diauxic shift drives an EtOH buffering by promoting an energy burst under stress, mainly in HTs. Analysis of mutants showed genes and lncRNAs in three strains critical for their EtOH tolerance. Finally, longevity, peroxisome, energy and lipid metabolisms, RNA/protein degradation and storage systems are the main pathways driving the EtOH tolerance phenotypes. ### Competing Interest Statement The authors have declared no competing interest.