Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production

Enxuan Jing; Brice Emanuelli; Matthew D Hirschey; Jeremie Boucher; Kevin Y Lee; David Lombard; Eric M Verdin; C Ronald Kahn

doi:10.1073/pnas.1111308108

Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production

Enxuan Jing, Brice Emanuelli, Matthew D Hirschey, Jeremie Boucher, Kevin Y Lee, David Lombard, Eric M Verdin, C Ronald Kahn

305 Citations (Scopus)

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.

Original language	English
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	108
Issue number	35
Pages (from-to)	14608-13
Number of pages	6
ISSN	0027-8424
DOIs	https://doi.org/10.1073/pnas.1111308108
Publication status	Published - 30 Aug 2011

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10.1073/pnas.1111308108

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Jing, E., Emanuelli, B., Hirschey, M. D., Boucher, J., Lee, K. Y., Lombard, D., Verdin, E. M., & Kahn, C. R. (2011). Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proceedings of the National Academy of Sciences of the United States of America, 108(35), 14608-13. https://doi.org/10.1073/pnas.1111308108

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 et al.

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

Jing, E, Emanuelli, B, Hirschey, MD, Boucher, J, Lee, KY, Lombard, D, Verdin, EM & Kahn, CR 2011, 'Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 35, pp. 14608-13. https://doi.org/10.1073/pnas.1111308108

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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.",

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author = "Enxuan Jing and Brice Emanuelli and Hirschey, {Matthew D} and Jeremie Boucher and Lee, {Kevin Y} and David Lombard and Verdin, {Eric M} and Kahn, {C Ronald}",

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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

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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

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DO - 10.1073/pnas.1111308108

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SN - 0027-8424

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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

IS - 35

ER -

Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production

Abstract

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