Balanced CoQ 6 biosynthesis is required for lifespan and mitophagy in yeast.

Autor: González-Mariscal I; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain., Martín-Montalvo A; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain., Ojeda-González C; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain., Rodríguez-Eguren A; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain., Gutiérrez-Ríos P; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain., Navas P; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain., Santos-Ocaña C; Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain.
Jazyk: angličtina
Zdroj: Microbial cell (Graz, Austria) [Microb Cell] 2017 Feb 03; Vol. 4 (2), pp. 38-51. Date of Electronic Publication: 2017 Feb 03.
DOI: 10.15698/mic2017.02.556
Abstrakt: Coenzyme Q is an essential lipid with redox capacity that is present in all organisms. In yeast its biosynthesis depends on a multiprotein complex in which Coq7 protein has both catalytic and regulatory functions. Coq7 modulates CoQ 6 levels through a phosphorylation cycle, where dephosphorylation of three amino acids (Ser/Thr) by the mitochondrial phosphatase Ptc7 increases the levels of CoQ 6 . Here we analyzed the role of Ptc7 and the phosphorylation state of Coq7 in yeast mitochondrial function. The conversion of the three Ser/Thr to alanine led to a permanently active form of Coq7 that caused a 2.5-fold increase of CoQ 6 levels, albeit decreased mitochondrial respiratory chain activity and oxidative stress resistance capacity. This resulted in an increase in endogenous ROS production and shortened the chronological life span (CLS) compared to wild type. The null PTC7 mutant ( ptc7 ∆) strain showed a lower biosynthesis rate of CoQ 6 and a significant shortening of the CLS. The reduced CLS observed in ptc7 Δ was restored by the overexpression of PTC7 but not by the addition of exogenous CoQ 6 . Overexpression of PTC7 increased mitophagy in a wild type strain. This finding suggests an additional Ptc7 function beyond the regulation of CoQ biosynthesis. Genetic disruption of PTC7 prevented mitophagy activation in conditions of nitrogen deprivation. In brief, we show that, in yeast, Ptc7 modulates the adaptation to respiratory metabolism by dephosphorylating Coq7 to supply newly synthesized CoQ 6 , and by activating mitophagy to remove defective mitochondria at stationary phase, guaranteeing a proper CLS in yeast.
Competing Interests: Conflict of interest: The authors declare no conflict of interest.
Databáze: MEDLINE
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