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United States Department of Agriculture

Agricultural Research Service

Research Project: MOLECULAR, CELLULAR, AND REGULATORY ASPECTS OF OBESITY DEVELOPMENT IN CHILDREN

Location: Children's Nutrition Research Center

Title: Nad(+) Dependent Deacetylase Sirt3 Regulates Mitochondrial Protein Synthesis by Deacetylation of the Ribosomal Protein Mrpl10

Authors
item Yang, Yongjie -
item Cimen, Huseyin -
item Han, Min-Joon -
item Shi, Tong -
item Deng, Jian-Hong -
item Koc, Hasan -
item Palacios, Orsolya -
item Montier, Laura -
item Bai, Yidong -
item Tong, Qiang -
item Koc, Emine -

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 3, 2009
Publication Date: March 5, 2010
Citation: Yang, Y., Cimen, H., Han, M., Shi, T., Deng, J., Koc, H., Palacios, O.M., Montier, L., Bai, Y., Tong, Q., Koc, E.C. 2010. NAD (+)- dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10. Journal of Biological Chemistry. 285(10):7417-7429.

Interpretive Summary: The mitochondrially localized SIRT3 deacetylase is important for the regulation of mitochondrial metabolism. In this study, we identified mitochondrial ribosomal protein L10 (MRPL10) as the major acetylated protein in the mitochondrial ribosome. We also found SIRT3 protein is associated with mitochondrial ribosome and is responsible for the deacetylation (removal of acetyl group from protein) of MRPL10. We observed that the increased acetylation of MRPL10 led to an increase in translational activity of mitochondrial ribosomes in mice deficient of SIRT3. In a similar manner, forced expression or knockdown of SIRT3 in muscle cells resulted in the suppression or enhancement of mitochondrial protein synthesis, respectively. Our findings provide the first evidence for the regulation of mitochondrial protein synthesis by the reversible acetylation of the mitochondrial ribosome and characterize MRPL10 as a novel substrate of SIRT3.

Technical Abstract: A member of the sirtuin family of NAD (+)-dependent deacetylases, SIRT3, is located in mammalian mitochondria and is important for regulation of mitochondrial metabolism, cell survival, and longevity. In this study, MRPL10 (mitochondrial ribosomal protein L10) was identified as the major acetylated protein in the mitochondrial ribosome. Ribosome-associated SIRT3 was found to be responsible for deacetylation of MRPL10 in an NAD (+)-dependent manner. We mapped the acetylated Lys residues, by tandem mass spectrometry and determined the role of these residues in acetylation of MRPL10 by site-directed mutagenesis. Furthermore, we observed that the increased acetylation of MRPL10 led to an increase in translational activity of mitochondrial ribosomes in Sirt3 (-/-) mice. In a similar manner, ectopic expression and knockdown of SIRT3 in C2C12 cells resulted in the suppression and enhancement of mitochondrial protein synthesis, respectively. Our findings constitute the first evidence for the regulation of mitochondrial protein synthesis, by the reversible acetylation of the mitochondrial ribosome and characterize MRPL10 as a novel substrate of the NAD (+)-dependent deacetylase, SIRT3.

Last Modified: 4/19/2014
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