The yeast Ptc7p mitochondrial phosphatase, the crossroad of coenzyme Q biosynthesis, mitophagy activation and chronological life span extension

Abstract

Resumen del póster presentado al 22nd IUBMB & 37th FEBS Congress, celebrado en Sevilla (España) del 4 al 9 de septiembre de 2012.-- et al.Coenzyme Q (CoQ or Q) is an essential isoprenylated benzoquinone component of mitochondria, which functions mainly as an electron carrier from complex I, or II to complex III at the inner membrane, and as an antioxidant particularly on lipoproteins and plasma membrane. CoQ biosynthesis is a highly regulated process driven by a multi-protein complex that catalyzes the modifications of the benzene ring. Coq7p/Cat5p (Coq7p) catalyzes one of the latest steps required for the final conversion of the late intermediate demethoxy-Q6 (DMQ6) to Q6, which also represents a key regulatory step in this pathway. Coq7p dephosphorylation was produced by the mitochondrial Ptc7 protein Ser/Thr phosphatase that activates aerobic yeast metabolism by regulating coenzyme Q (CoQ) biosynthesis. Yeast lacking PTC7 (YHR076w) gene exhibited decreased of both mitochondrial function and oxidative stress defenses, leading to increased protein carbonylation damage. CoQ content was decreased in PTC7 deleted strain, suggesting that during respiratory metabolism Ptc7p activates the CoQ6 biosynthesis. Ptc7p dephosphorylates Coq7p in both in vivo and in vitro assays. PTC7 null mutant exhibited increased Coq7p phosphorylation when CoQ biosynthesis was induced. Chronological life span (CLS) is defined as a survival mechanism that depends on metabolic and stress adaptations to environment. PTC7 strain showed a decreased CLS that was not rescued by exogenous CoQ6. Rescue of CLS required Ptc7p that also activated mitophagy but not macroautophagy. These results led us to propose that Ptc7p links homeostasis of CoQ by regulating its biosynthesis through the phosphorylation stage of Coq7p and mitochondrial recycling as an adaptation mechanism to both stress and nutritional environment changes to promote CLS.Peer reviewe