Toward the discovery of biological functions associated with the mechanosensor Mtl1p of Saccharomyces cerevisiae via integrative multi-OMICs analysis.

ABSTRACT: Functional analysis of the Mtl1 protein in Saccharomyces cerevisiae has revealed that this transmembrane sensor endows yeast cells with resistance to oxidative stress by hydrogen peroxide (H2O2) treatment through a signaling mechanism called the cell wall integrity pathway (CWI). Quantitative mRNA expression analysis revealed that genes containing the Stress Response Element (STRE) element 5’-AGGGG-3’, a regulatory sequence recognized by activating Transcription Factors (TFs) Msn2 and Msn4, were transcriptionally repressed by 2-fold or greater in the mtl1Δ strains. Since these TFs are negatively regulated by PKA, this observation suggests that Mtl1p signaling modulates the inhibitory activity of PKA over the transcription of specific stress response genes. Upregulation of multiple heat shock proteins (HSPs) and the phosphatase subunit of trehalose 6-phosphate synthase suggests that mtl1Δ strains undergo intrinsic activation of a non-lethal heat stress response, which appears to be controlled by Mtl1p. Furthermore, quantitative global proteomic analysis of TMT-labeled proteins combined with metabolome analysis revealed that mtl1Δ strains exhibit decreased levels of metabolites of carboxylic acid metabolism, decreased expression of anabolic enzymes and increased expression of catabolic enzymes involved in the metabolism of amino acids, and enhanced expression of mitochondrial respirasome proteins. These observations support the notion that Mtl1p has an important role in metabolic regulatory mechanisms linked to TORC1 that are required to maintain cellular homeostasis and optimal mitochondrial function.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Abiel Roche  

LAB HEAD: Dr. Abiel Roche-Lima

PROVIDER: PXD023963 | Pride | 2021-09-10

REPOSITORIES: Pride