Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 288, Issue 40, Pages 29036-29045Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.486753
Keywords
Acetyl Coenzyme A; Metabolic Diseases; Metabolic Regulation; Mitochondrial Metabolism; pH Regulation; Sirtuins; Acetylation; Nonenzymatic; Succinyl Coenzyme A; Succinylation
Categories
Funding
- National Institutes of Health [1P01HL085098]
- American Heart Association [0855646G, 11PRE7290079]
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Alterations in mitochondrial protein acetylation are implicated in the pathophysiology of diabetes, the metabolic syndrome, mitochondrial disorders, and cancer. However, a viable mechanism responsible for the widespread acetylation in mitochondria remains unknown. Here, we demonstrate that the physiologic pH and acyl-CoA concentrations of the mitochondrial matrix are sufficient to cause dose- and time-dependent, but enzyme-independent acetylation and succinylation of mitochondrial and nonmitochondrial proteins in vitro. These data suggest that protein acylation in mitochondria may be a chemical event facilitated by the alkaline pH and high concentrations of reactive acyl-CoAs present in the mitochondrial matrix. Although these results do not exclude the possibility of enzyme-mediated protein acylation in mitochondria, they demonstrate that such a mechanism may not be required in its unique chemical environment. These findings may have implications for the evolutionary roles that the mitochondria-localized SIRT3 deacetylase and SIRT5 desuccinylase have in the maintenance of metabolic health.
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