SIRT5 deacetylates and activates urate oxidase in liver mitochondria of mice

We identified urate oxidase (UOX) as a target of SIRT5 by comparing mitochondrial proteins in livers of SIRT5-overexpressing transgenic (SIRT5 Tg) and wild-type mice by using two-dimensional electrophoresis. Acetylation levels of UOX in liver of SIRT5 Tg mice were approximately half of those in wild-type mice, and UOX activity was significantly increased. In vitro-synthesized UOX protein was acetylated when incubated with mitochondria from wild-type mice liver but the levels were less when incubated with those from SIRT5 Tg mice liver. These results suggest that SIRT5 activates UOX through deacetylation in mouse liver mitochondria.