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T or1, S ch9 and PKA downregulation in quiescence rely on M tl1 to preserve mitochondrial integrity and cell survival
Author(s) -
Sundaram Venkatraghavan,
Petkova Mima I.,
PujolCarrion Nuria,
Boada Jordi,
TorreRuiz Maria Angeles
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13013
Subject(s) - biology , downregulation and upregulation , mitochondrion , microbiology and biotechnology , personal integrity , cell survival , cell , computational biology , cell culture , genetics , gene , psychology , social psychology
Summary Here we show that M tl1, member of the cell wall integrity pathway of S accharomyces cerevisiae , plays a positive role in chronological life span ( CLS ). The absence of M tl1 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. M tl1 also plays a role in the regulation of both B cy1 stability and phosphorylation, mainly in response to glucose depletion. In postdiauxic phase and in conditions of glucose depletion, M tl1 negatively regulates TOR1 function leading to S ch9 inactivation and B cy1 phosphorylation converging in PKA inhibition. S lt2/ M pk1 kinase partially contributes to B cy1 phosphorylation, although additional targets are not excluded. M tl1 links mitochondrial dysfunction with TOR and PKA pathways in quiescence, glucose being the main signalling molecule.