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NAD+‐dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of mitochondrial ribosomal protein L10
Author(s) -
Koc Emine C,
Yang Yongjie,
Cimen Huseyin,
Han MinJoon,
Tong Shi,
Deng JianHong,
Koc Hasan,
Palacios Orsolya M,
Montier Laura,
Bai Yidong
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.467.2
Subject(s) - sirt3 , acetylation , sirtuin , nad+ kinase , mitochondrion , biochemistry , ribosomal protein , mitochondrial ribosome , chemistry , biology , microbiology and biotechnology , ribosome , enzyme , rna , gene
Reversible acetylation regulates many biological processes including mitochondrial energy metabolism, cell survival and longevity. A member of the sirtuin family of NAD + ‐dependent deacetylases, SIRT3, is important for regulation of reversible acetylation in mammalian mitochondria. In this study, we identified ribosomal MRPL10 as one of the major acetylated proteins 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 lead to an increase in translational activity of mitochondrial ribosomes in SIRT3 −/− mice. In a similar manner, ectopic expression and knock‐down 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. Supported by NIH R01s to ECK ( GM071034 ), YB ( AG025223 ), and QT ( DK075978 ).