Tor1, Sch9 and PKA downregulation in quiescence rely on Mtl1 to preserve mitochondrial integrity and cell survival

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2015-07-22
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Sundaram, Venkatraghavan
Ivanova Petkova, Mima
Pujol Carrión, NúriaPujol Carrión, Núria - ORCID ID
Boada Pallàs, JordiBoada Pallàs, Jordi - ORCID ID
Torre Ruiz, M. A. de laTorre Ruiz, M. A. de la - ORCID ID
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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.
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http://hdl.handle.net/10459.1/49261
DOI
https://doi.org/10.1111/mmi.13013
Journal or Serie
Molecular Microbiology, 2015, vol. 97, num. 1, p. 93-109
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Articles publicats (Ciències Mèdiques Bàsiques)
Articles publicats (Grup de Recerca en Estrès Cel·lular i Supervivència en Models Eucariotes)
Articles publicats (Grup de Recerca en Fisiopatologia Metabòlica)
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Articles publicats (Medicina Experimental)
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