has become a novel target pursued substantially for its involvement in regulation of aging and agerelated diseases, possibly due to its well-known association with exceptionally long lifespan in humans as well as its mitochondrial localization (5).
Sodium fluoride induces nephrotoxicity via oxidative stress-regulated mitochondrial SIRT3
[5.] Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, Gupta MP: Sirt3
blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice.
D'Cunha, "Minnelide/Triptolide impairs mitochondrial function by regulating SIRT3
in P53-dependent manner in non-small cell lung cancer," PLoS One, vol.
It is 200-500fold more selective for SIRT1 than for SIRT2, SIRT3
, or SIRT6, has a half-life of 2h, and is active in <100 nM concentrations .
Meng et al., "Acetylation-dependent regulation of mitochondrial ALDH2 activation by SIRT3
mediates acute ethanol-induced eNOS activation," FEBS Letters, vol.
Notably, the distribution of some isoforms (e.g., SIRT1, SIRT2, SIRT3
, and SIRT5) is varied due to their specific activity .
PGC-1[alpha] targets SIRT3
, a mitochondrial deacetylase, which promotes mitochondrial biogenesis, suppression of ROS , and mitochondrial FA oxidation .
Keffler et al., "SIRT3
deacetylates ceramide synthases: Implications for mitochondrial dysfunction and brain injury," The Journal of Biological Chemistry, vol.
Three key enzymes involved in the sensing of these perturbations and the subsequent induction of signal transduction are AMP-activated protein kinase (AMPK) and silent mating type information regulation 2 homologues 1 and 3 (SIRT1 and SIRT3
Shi et al., "Activation of the aryl hydrocarbon receptor sensitizes mice to nonalcoholic steatohepatitis by deactivating mitochondrial sirtuin deacetylase Sirt3
," Molecular and cellular biology, vol.