NAD+-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10

J Biol Chem. 2010 Mar 5;285(10):7417-29. doi: 10.1074/jbc.M109.053421. Epub 2009 Dec 30.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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*
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / metabolism*
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Interference
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Sequence Alignment
  • Sirtuin 3 / chemistry
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism*
  • Two-Hybrid System Techniques


  • MRPL10 protein, mouse
  • Mitochondrial Proteins
  • Peptides
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Ribosomal Proteins
  • NAD
  • Sirtuin 3