Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity.

Lydia W S Finley, Wilhelm Haas, Valérie Desquiret-Dumas, Douglas C Wallace, Vincent Procaccio, Steven P Gygi, Marcia C Haigis

Department of Pathology, The Paul F. Glenn Labs for the Biological Mechanisms of Aging, Harvard Medical School, Boston, Massachusetts, United States of America.

PloS one 2011

filter terms:

Sirtuins (SIRT1-7) are a family of NAD-dependent deacetylases and/or ADP-ribosyltransferases that are involved in metabolism, stress responses and longevity. SIRT3 is localized to mitochondria, where it deacetylates and activates a number of enzymes involved in fuel oxidation and energy production. In this study, we performed a proteomic screen to identify SIRT3 interacting proteins and identified several subunits of complex II and V of the electron transport chain. Two subunits of complex II (also known as succinate dehydrogenase, or SDH), SDHA and SDHB, interacted specifically with SIRT3. Using mass spectrometry, we identified 13 acetylation sites on SDHA, including six novel acetylated residues. SDHA is hyperacetylated in SIRT3 KO mice and SIRT3 directly deacetylates SDHA in a NAD-dependent manner. Finally, we found that SIRT3 regulates SDH activity both in cells and in murine brown adipose tissue. Our study identifies SDHA as a binding partner and substrate for SIRT3 deacetylase activity. SIRT3 loss results in decreased SDH enzyme activity, suggesting that SIRT3 may be an important physiological regulator of SDH activity.

Citation

Lydia W S Finley, Wilhelm Haas, Valérie Desquiret-Dumas, Douglas C Wallace, Vincent Procaccio, Steven P Gygi, Marcia C Haigis. Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. PloS one. 2011;6(8):e23295