title: Tor1, Sch9 and PKA downregulation in quiescence rely on Mtl1 to preserve mitochondrial integrity and cell survival.
abstract: Here we show that Mtl1, member of the cell wall integrity pathway of Saccharomyces cerevisiae, plays a positive role in chronological life span (CLS). The absence of Mtl1 shortens CLS and causes impairment in the mitochondrial function. This is reflected in a descent in oxygen consumption during the postdiauxic state, an increase in the uncoupled respiration and mitochondrial membrane potential and also a descent in aconitase activity. We demonstrate that all these effects are a consequence of signalling defects suppressed by TOR1 (target of rapamycin) and SCH9 deletion and less efficiently by Protein kinase A (PKA) inactivation. Mtl1 also plays a role in the regulation of both Bcy1 stability and phosphorylation, mainly in response to glucose depletion. In postdiauxic phase and in conditions of glucose depletion, Mtl1 negatively regulates TOR1 function leading to Sch9 inactivation and Bcy1 phosphorylation converging in PKA inhibition. Slt2/Mpk1 kinase partially contributes to Bcy1 phosphorylation, although additional targets are not excluded. Mtl1 links mitochondrial dysfunction with TOR and PKA pathways in quiescence, glucose being the main signalling molecule.
authors: Department of Basic Medical Sciences, IRB-Lleida, University of Lleida, Av. Alcalde Rovira Roure n° 80, 25198, Lleida, Spain.
authors: Venkatraghavan
authors: V
authors: Sundaram
authors: Department of Basic Medical Sciences, IRB-Lleida, University of Lleida, Av. Alcalde Rovira Roure n° 80, 25198, Lleida, Spain.
authors: Mima I
authors: MI
authors: Petkova
authors: Department of Basic Medical Sciences, IRB-Lleida, University of Lleida, Av. Alcalde Rovira Roure n° 80, 25198, Lleida, Spain.
authors: Nuria
authors: N
authors: Pujol-Carrion
authors: Department of Experimental Medicine, IRB-Lleida, University of Lleida, Av. Alcalde Rovira Roure n° 80, 25198, Lleida, Spain.
authors: Jordi
authors: J
authors: Boada
authors: Department of Basic Medical Sciences, IRB-Lleida, University of Lleida, Av. Alcalde Rovira Roure n° 80, 25198, Lleida, Spain.
authors: Maria Angeles
authors: MA
authors: de la Torre-Ruiz
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D050296:Microbial Viability; D008928:Mitochondria / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000154:Aconitate Hydratase; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D018631:ras Proteins; C550933:Mtl1 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C530964:SCH9 protein, S cerevisiae