Heat stress increases global mitochondrial protein acetylation and steady state levels of SIRT3 (LB798)

Aging results in exacerbated mitochondrial damage and cellular dysfunction after exposure to physiological challenges such as heat stress. Additionally, induction of mitochondrial stress‐defense proteins is blunted after heat stress with aging. The sirtuins are deacetylase enzymes implicated in stress defense and longevity. Sirtuin‐3 (SIRT3), which has been shown to reduce oxidative injury, is a mitochondrial enzyme that deacetylates mitochondrial proteins. Since little is known about the response of hepatic SIRT3 to physiological stress, the goal of the present study was to characterize protein levels of SIRT3 in young (6 mo) and old (24 mo) Fischer 344 rats after heat stress. Animals were exposed to a two‐heat stress protocol, and liver mitochondria were isolated at 2 and 24 h after the second heat stress. Nonheated animals served as controls. SIRT3 protein expression and global protein acetylation were determined by immunoblot analysis. Aging was associated with an increase in SIRT3 protein, and a trend for a decrease in protein acetylation. In each of the two age groups, heat stress increased both SIRT3 and global protein acetylation, which suggests that the increase in protein acetylation overwhelms the deacetylase activity of SIRT3. The increase in SIRT3 suggests that it is a stress‐responsive protein and warrants further inquiry into the acetylation status of selected mitochondrial proteins. Grant Funding Source : Supported by NIH R01 AG‐12350