Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production
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Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. / Jing, Enxuan; Emanuelli, Brice; Hirschey, Matthew D; Boucher, Jeremie; Lee, Kevin Y; Lombard, David; Verdin, Eric M; Kahn, C Ronald.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 35, 30.08.2011, p. 14608-13.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production
AU - Jing, Enxuan
AU - Emanuelli, Brice
AU - Hirschey, Matthew D
AU - Boucher, Jeremie
AU - Lee, Kevin Y
AU - Lombard, David
AU - Verdin, Eric M
AU - Kahn, C Ronald
PY - 2011/8/30
Y1 - 2011/8/30
N2 - 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.
AB - 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.
KW - Aging
KW - Animals
KW - Cells, Cultured
KW - Diabetes Mellitus, Experimental
KW - Insulin Receptor Substrate Proteins
KW - Insulin Resistance
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mitochondria
KW - Muscle, Skeletal
KW - Myoblasts
KW - Oxidation-Reduction
KW - Phosphorylation
KW - Reactive Oxygen Species
KW - Signal Transduction
KW - Sirtuin 3
U2 - 10.1073/pnas.1111308108
DO - 10.1073/pnas.1111308108
M3 - Journal article
C2 - 21873205
VL - 108
SP - 14608
EP - 14613
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 35
ER -
ID: 143328453