NAD+-dependent Deacetylase SIRT3 Regulates Mitochondrial Protein Synthesis by Deacetylation of the Ribosomal Protein MRPL10

• Published in: The Journal of biological chemistry 2010-03, Vol.285 (10), p.7417-7429
• Main Authors: Yang, Yongjie, Cimen, Huseyin, Han, Min-Joon, Shi, Tong, Deng, Jian-Hong, Koc, Hasan, Palacios, Orsolya M., Montier, Laura, Bai, Yidong, Tong, Qiang, Koc, Emine C.
• Format: Article
• Language: English
• Subjects: Acetylation; Amino Acid Sequence; Animals; Cattle; Cell Line; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria - metabolism; Mitochondrial Proteins - chemistry; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Mitochondrial Ribosomal Protein MRPL10; Models, Molecular; Molecular Sequence Data; NAD - metabolism; Peptides - genetics; Peptides - metabolism; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Synthesis and Degradation; Protein/Post-translational Modification; Protein/Synthesis; Proteomics; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Ribosomal Proteins - chemistry; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; RNA Interference; RNA/Ribosome Function; Sequence Alignment; SIRT3; Sirtuin 3 - chemistry; Sirtuin 3 - genetics; Sirtuin 3 - metabolism; Subcellular Organelles/Mitochondria; Translation; Translation/Regulation Eukaryote; Two-Hybrid System Techniques
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.053421

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.