Ptc7p Dephosphorylates Select Mitochondrial Proteins to Enhance Metabolic Function

Autor: Xiao Guo, Natalie M. Niemi, Paul D. Hutchins, Samson G.F. Condon, Adam Jochem, Arne Ulbrich, Alan J. Higbee, Jason D. Russell, Alessandro Senes, Joshua J. Coon, David J. Pagliarini
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cell Reports, Vol 18, Iss 2, Pp 307-313 (2017)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.12.049
Popis: Summary: Proper maintenance of mitochondrial activity is essential for metabolic homeostasis. Widespread phosphorylation of mitochondrial proteins may be an important element of this process; yet, little is known about which enzymes control mitochondrial phosphorylation or which phosphosites have functional impact. We investigate these issues by disrupting Ptc7p, a conserved but largely uncharacterized mitochondrial matrix PP2C-type phosphatase. Loss of Ptc7p causes respiratory growth defects concomitant with elevated phosphorylation of select matrix proteins. Among these, Δptc7 yeast exhibit an increase in phosphorylation of Cit1p, the canonical citrate synthase of the tricarboxylic acid (TCA) cycle, that diminishes its activity. We find that phosphorylation of S462 can eliminate Cit1p enzymatic activity likely by disrupting its proper dimerization, and that Ptc7p-driven dephosphorylation rescues Cit1p activity. Collectively, our work connects Ptc7p to an essential TCA cycle function and to additional phosphorylation events that may affect mitochondrial activity inadvertently or in a regulatory manner. : Mitochondrial phosphorylation is abundant and dynamic, yet its regulation and contribution to organellar function is poorly understood. To address this, Guo et al. coupled quantitative phosphoproteomics with classic biochemistry to study the mitochondrial phosphatase Ptc7p. They find that Ptc7p deletion perturbs mitochondrial phosphorylation, partially inactivates citrate synthase, and decreases organellar function. Keywords: Ptc7, Pptc7, mitochondria, phosphatase, phosphoproteomics, mitochondrial phosphorylation, citrate synthase
Databáze: Directory of Open Access Journals