title: SIRT3 deacetylates ATP synthase F1 complex proteins in response to nutrient- and exercise-induced stress.
abstract: OBJECTIVE
  Adenosine triphosphate (ATP) synthase uses chemiosmotic energy across the inner mitochondrial membrane to convert adenosine diphosphate and orthophosphate into ATP, whereas genetic deletion of Sirt3 decreases mitochondrial ATP levels. Here, we investigate the mechanistic connection between SIRT3 and energy homeostasis.
  
  
  RESULTS
  By using both in vitro and in vivo experiments, we demonstrate that ATP synthase F1 proteins alpha, beta, gamma, and Oligomycin sensitivity-conferring protein (OSCP) contain SIRT3-specific reversible acetyl-lysines that are evolutionarily conserved and bind to SIRT3. OSCP was further investigated and lysine 139 is a nutrient-sensitive SIRT3-dependent deacetylation target. Site directed mutants demonstrate that OSCP(K139) directs, at least in part, mitochondrial ATP production and mice lacking Sirt3 exhibit decreased ATP muscle levels, increased ATP synthase protein acetylation, and an exercise-induced stress-deficient phenotype.
  
  
  METHODS
  This work connects the aging and nutrient response, via SIRT3 direction of the mitochondrial acetylome, to the regulation of mitochondrial energy homeostasis under nutrient-stress conditions by deacetylating ATP synthase proteins.
  
  
  CONCLUSIONS
  Our data suggest that acetylome signaling contributes to mitochondrial energy homeostasis by SIRT3-mediated deacetylation of ATP synthase proteins.
authors.affiliation: 1 Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, Illinois.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Vassilopoulos
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Pennington
authors.forename: Thorkell
authors.initials: T
authors.lastname: Andresson
authors.forename: David M
authors.initials: DM
authors.lastname: Rees
authors.forename: Allen D
authors.initials: AD
authors.lastname: Bosley
authors.forename: Ian M
authors.initials: IM
authors.lastname: Fearnley
authors.forename: Amy
authors.initials: A
authors.lastname: Ham
authors.forename: Charles Robb
authors.initials: CR
authors.lastname: Flynn
authors.forename: Salisha
authors.initials: S
authors.lastname: Hill
authors.forename: Kristie Lindsey
authors.initials: KL
authors.lastname: Rose
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
authors.forename: John E
authors.initials: JE
authors.lastname: Walker
authors.forename: David
authors.initials: D
authors.lastname: Gius
mesh_terms: D025181:ATP Synthetase Complexes / Q000378:metabolism*; D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D025261:Mitochondrial Proton-Translocating ATPases; D018482:Muscle, Skeletal / Q000378:metabolism; D010805:Physical Conditioning, Animal; D011485:Protein Binding; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D000255:Adenosine Triphosphate; D025181:ATP Synthetase Complexes; D056566:Sirtuin 3; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; C020439:oligomycin sensitivity-conferring protein