title: Balanced CoQ6biosynthesis is required for lifespan and mitophagy in yeast.
abstract: 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 CoQ6levels through a phosphorylation cycle, where dephosphorylation of three amino acids (Ser/Thr) by the mitochondrial phosphatase Ptc7 increases the levels of CoQ6. 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 CoQ6levels, 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 nullPTC7mutant (ptc7∆) strain showed a lower biosynthesis rate of CoQ6and a significant shortening of the CLS. The reduced CLS observed inptc7Δ was restored by the overexpression ofPTC7but not by the addition of exogenous CoQ6. Overexpression ofPTC7increased mitophagy in a wild type strain. This finding suggests an additional Ptc7 function beyond the regulation of CoQ biosynthesis. Genetic disruption ofPTC7prevented 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 CoQ6, and by activating mitophagy to remove defective mitochondria at stationary phase, guaranteeing a proper CLS in yeast.
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Mariscal
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain.
authors.forename: Aléjandro
authors.initials: A
authors.lastname: Martín-Montalvo
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ojeda-González
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Rodríguez-Eguren
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: Gutiérrez-Ríos
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain.
authors.forename: Plácido
authors.initials: P
authors.lastname: Navas
authors.affiliation: Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, 41013, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Santos-Ocaña
keywords: chronological life span; coenzyme Q6; mitochondria; mitophagy; regulation; yeast