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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Proceedings of the National Academy of Sciences of the United States of America
Vol/bind	108
Udgave nummer	35
Sider (fra-til)	14608-13
Antal sider	6
ISSN	0027-8424
DOI	https://doi.org/10.1073/pnas.1111308108
Status	Udgivet - 30 aug. 2011

Emneord

Aging
Animals
Cells, Cultured
Diabetes Mellitus, Experimental
Insulin Receptor Substrate Proteins
Insulin Resistance
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria
Muscle, Skeletal
Myoblasts
Oxidation-Reduction
Phosphorylation
Reactive Oxygen Species
Signal Transduction
Sirtuin 3

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Adgang til dokumentet

10.1073/pnas.1111308108

Citationsformater

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.

I: Proceedings of the National Academy of Sciences of the United States of America, Bind 108, Nr. 35, 30.08.2011, s. 14608-13.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › 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, bind 108, nr. 35, s. 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}",

year = "2011",

month = aug,

day = "30",

doi = "10.1073/pnas.1111308108",

language = "English",

volume = "108",

pages = "14608--13",

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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

U2 - 10.1073/pnas.1111308108

DO - 10.1073/pnas.1111308108

M3 - Journal article

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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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FN’s Verdensmål

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