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•Reversible lysine acetylation has emerged as a key regulator of mitochondrial fatty acid oxidation and antioxidant defense.•Sirtuin 3 is the primary mitochondrial deacetylase, but is downregulated in obesity, resulting in mitochondrial protein hyperacetylation.•Animals lacking sirtuin 3 display accelerated weight gain and development of the metabolic syndrome on a high fat diet.•Whether restoration...
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