Mitochondrial sirtuins.
Sirtuins have emerged as important proteins in aging, stress resistance and metabolic regulation. Three sirtuins, SIRT3, 4 and 5, are located within the mitochondrial matrix. SIRT3 and SIRT5 are NAD(+)-dependent deacetylases that remove acetyl groups from acetyllysine-modified proteins and yield 2'-O-acetyl-ADP-ribose and nicotinamide. SIRT4 can transfer the ADP-ribose group from NAD(+) onto acceptor proteins. Recent findings reveal that a large fraction of mitochondrial proteins are acetylated and that mitochondrial protein acetylation is modulated by nutritional status. This and the identification of targets for SIRT3, 4 and 5 support the model that mitochondrial sirtuins are metabolic sensors that modulate the activity of metabolic enzymes via protein deacetylation or mono-ADP-ribosylation. Here, we review and discuss recent progress in the study of mitochondrial sirtuins and their targets.
Huang
Jing-Yi
JY
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA, USA.
Hirschey
Matthew D
MD
Shimazu
Tadahiro
T
Ho
Linh
L
Verdin
Eric
E
D000107:Acetylation; D000818:Animals; D056545:Group III Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D038961:O-Acetyl-ADP-Ribose / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism*
D024101:Mitochondrial Proteins; D038961:O-Acetyl-ADP-Ribose; D009243:NAD; D056545:Group III Histone Deacetylases; D056566:Sirtuin 3; D037761:Sirtuins