Ahn, B. H. et al. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc. Natl Acad. Sci. USA 105, 14447-14452
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 10/2008; 105(38):14447-52. DOI: 10.1073/pnas.0803790105
Here, we demonstrate a role for the mitochondrial NAD-dependent deacetylase Sirt3 in the maintenance of basal ATP levels and as a regulator of mitochondrial electron transport. We note that Sirt3(-/-) mouse embryonic fibroblasts have a reduction in basal ATP levels. Reconstitution with wild-type but not a deacetylase-deficient form of Sirt3 restored ATP levels in these cells. Furthermore in wild-type mice, the resting level of ATP correlates with organ-specific Sirt3 protein expression. Remarkably, in mice lacking Sirt3, basal levels of ATP in the heart, kidney, and liver were reduced >50%. We further demonstrate that mitochondrial protein acetylation is markedly elevated in Sirt3(-/-) tissues. In addition, in the absence of Sirt3, multiple components of Complex I of the electron transport chain demonstrate increased acetylation. Sirt3 can also physically interact with at least one of the known subunits of Complex I, the 39-kDa protein NDUFA9. Functional studies demonstrate that mitochondria from Sirt3(-/-) animals display a selective inhibition of Complex I activity. Furthermore, incubation of exogenous Sirt3 with mitochondria can augment Complex I activity. These results implicate protein acetylation as an important regulator of Complex I activity and demonstrate that Sirt3 functions in vivo to regulate and maintain basal ATP levels.
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- "Sirtuin3 (SIRT3) plays an important role in maintaining mitochondrial redox balance . SIRT3 physically interacts with at least one of the known subunits of Complex I, enhances activity by deacetylation, and reduces the formation of excess ROS . Cytochrome c (CYC) is another important component of the electron transport chain that helps control ROS leakage, and SIRT3 activity is required for CYC mRNA expression  . "
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- "Generally the protein complexes I–V of ETC and oxidative phosphorylation are found acetylated at 511 lysine residues (Kim et al., 2006). Various studies show that the two subunits NDUFA9 subunit of complex I of ETC and oligomycin sensitivity conferring protein (OSCP) of complex V of oxidative phosphorylation, which is found to be acetylated at lysine amino acid residue K139 (Ahn et al., 2008) physically interact with Sirt3. A study shows that the ATP5A1 and ATP5F1 subunits of complex V also interact with Sirt3 (Vassilopoulos et al., 2014). "
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