Functional analysis of the Mtl1 protein in Saccharomyces cerevisiae has revealed that this transmembrane sensor endows yeast cells with resistance to oxidative stress through a signaling mechanism called the cell wall integrity pathway (CWI). We observed upregulation of multiple heat shock proteins (HSPs), proteins associated with the formation of stress granules, and the phosphatase subunit of trehalose 6-phosphate synthase which suggests that mtl1Δ strains undergo intrinsic activation of a non-lethal heat stress response. Furthermore, quantitative global proteomic analysis conducted on 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, with enhanced expression of mitochondrial respirasome proteins. These observations support the idea that Mtl1 protein controls the suppression of a non-lethal heat stress response under normal conditions while it plays an important role in metabolic regulatory mechanisms linked to TORC1 signaling that are required to maintain cellular homeostasis and optimal mitochondrial function.
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This work was conducted with support from Core facilities: Metabolomics Research Facility sponsored by PR-INBRE; Translational Proteomics Center sponsored by the RCMI-CCRHD, PR-INBRE, and UPR Comprehensive Cancer Center; and Integrated Informatics Services Core, sponsored by RCMI, funded by NIH Grants NIGMS 5P20GM103475 and NIMHHD U54MD007600. Student support was provided by NIGMS-RISE 5R25GM061838 to N. Martinez-Matias. Partial support was provided by the University of Puerto Rico to J.R. Rodriguez-Medina, the University of Kentucky to B. C. Rymond, Canadian Institutes of Health Research Grants (MOP-125952; RSN-124512, 132191; and FDN-154318) to M. Babu, and Ontario Genomics Institute, Canadian Cystic Fibrosis Foundation, Canadian Cancer Society, Pancreatic Cancer Canada and University Health Network to I. Stagljar.
Metabolomics data are available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench109 (Project ID PR001034, https://doi.org/10.21228/M81X28). RNAseq data are available at Sequence Read Archive (SRA) repository, with the accession number PRJNA686365 (https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA686365). Proteomics data are available at the Proteomics Identifications Database (PRIDE). Currently, it is only accessible for authors and reviewers (to access the data please go to https://www.ebi.ac.uk/pride/archive/login, and use these credentials to login User: firstname.lastname@example.org, Password: oPr4sZae, then look for the accession number PXD023963). The data will be publicly accessible after the paper is accepted for publication.
Martínez-Matías, Nelson; Chorna, Nataliya; González-Crespo, Sahily; Villanueva, Lilliam; Montes-Rodríguez, Ingrid; Melendez-Aponte, Loyda M.; Roche-Lima, Abiel; Carrasquillo-Carrión, Kelvin; Santiago-Cartagena, Ednalise; Rymond, Brian C.; Babu, Mohan; Stagljar, Igor; and Rodríguez-Medina, José R., "Toward the Discovery of Biological Functions Associated with the Mechanosensor Mtl1p of Saccharomyces cerevisiae via Integrative Multi-OMICs Analysis" (2021). Biology Faculty Publications. 206.