title: Ptc7p Dephosphorylates Select Mitochondrial Proteins to Enhance Metabolic Function.
abstract: 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.
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Guo
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Niemi
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, Madison, WI 53706, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Hutchins
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Samson G F
authors.initials: SGF
authors.lastname: Condon
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Jochem
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, Madison, WI 53706, USA.
authors.forename: Arne
authors.initials: A
authors.lastname: Ulbrich
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, Madison, WI 53706, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Higbee
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Genome Center of Wisconsin, Madison, WI 53706, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Russell
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Senes
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Coon
authors.affiliation: Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: dpagliarini@morgridge.org.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pagliarini
mesh_terms: D000332:Aerobiosis; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D055503:Protein Multimerization; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D024101:Mitochondrial Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D010768:Phosphoserine; C433364:PTC7 protein, S cerevisiae; D054648:Protein Phosphatase 2
keywords: Pptc7; Ptc7; citrate synthase; mitochondria; mitochondrial phosphorylation; phosphatase; phosphoproteomics