title: Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production.
abstract: Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling. This effect is mimicked by knockdown of Sirt3 in cultured myoblasts, which exhibit reduced mitochondrial oxidation, increased reactive oxygen species, activation of JNK, increased serine and decreased tyrosine phosphorylation of IRS-1, and decreased insulin signaling. Thus, Sirt3 plays an important role in diabetes through regulation of mitochondrial oxidation, reactive oxygen species production, and insulin resistance in skeletal muscle.
authors.affiliation: Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Enxuan
authors.initials: E
authors.lastname: Jing
authors.forename: Brice
authors.initials: B
authors.lastname: Emanuelli
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hirschey
authors.forename: Jeremie
authors.initials: J
authors.lastname: Boucher
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Lombard
authors.forename: Eric M
authors.initials: EM
authors.lastname: Verdin
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D056566:Sirtuin 3 / Q000502:physiology*
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D017382:Reactive Oxygen Species; C525046:Sirt3 protein, mouse; D056566:Sirtuin 3