Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation

Jin Hong, Bong Woo Kim, Hyo Jung Choo, Jung Jin Park, Jae Sung Yi, Dong Min Yu, Hyun Lee, Gye Soon Yoon, Jae Seon Lee, Young-Gyu Ko

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

To address whether mitochondrial biogenesis is essential for skeletal myogenesis, C2C12 myogenesis was investigated after knockdown of NADH dehydrogenase (ubiquintone) flavoprotein 1 (NDUFV1), which is an oxidative phosphorylation complex I subunit that is the first subunit to accept electrons from NADH. The NDUFVI knockdown enhanced C2C12 myogenesis by decreasing the NAD+/NADH ratio and subsequently inactivating SIRT1 and SIRT1 activators (pyruvate, SRT1720, and resveratrol) abolished the NDUFV1 knockdown-induced myogenesis enhancement. However, the insulin-elicited activation of insulin receptor β (IRβ) and insulin receptor substrate-1 (IRS-1) was reduced with elevated levels of protein-tyrosine phosphatase 1B after NDUFV1 knockdown in C2C12 myotubes. The NDUFV1 knockdown-induced blockage of insulin signaling was released by protein-tyrosine phosphatase 1B knockdown in C2C12 myotubes, and we found that NDUFV1 or SIRT1 knockdown did not affect mitochondria biogenesis during C2C12 myogenesis. Based on these data, we can conclude that complex I dysfunction-induced SIRT1 inactivation leads to myogenesis enhancement but blocks insulin signaling without affecting mitochondria biogenesis.

Original languageEnglish
Pages (from-to)20012-20025
Number of pages14
JournalJournal of Biological Chemistry
Volume289
Issue number29
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

NADH Dehydrogenase
Flavoproteins
Muscle Development
Insulin
Non-Receptor Type 1 Protein Tyrosine Phosphatase
NAD
Mitochondria
Skeletal Muscle Fibers
Insulin Receptor Substrate Proteins
Insulin Receptor
Pyruvic Acid
Oxidative Phosphorylation
Organelle Biogenesis
Chemical activation
Mitochondrial complex I deficiency
Electrons

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation. / Hong, Jin; Kim, Bong Woo; Choo, Hyo Jung; Park, Jung Jin; Yi, Jae Sung; Yu, Dong Min; Lee, Hyun; Yoon, Gye Soon; Lee, Jae Seon; Ko, Young-Gyu.

In: Journal of Biological Chemistry, Vol. 289, No. 29, 01.01.2014, p. 20012-20025.

Research output: Contribution to journalArticle

Hong, Jin ; Kim, Bong Woo ; Choo, Hyo Jung ; Park, Jung Jin ; Yi, Jae Sung ; Yu, Dong Min ; Lee, Hyun ; Yoon, Gye Soon ; Lee, Jae Seon ; Ko, Young-Gyu. / Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 29. pp. 20012-20025.
@article{6d25a7c517ae4c8cba8913d35eca86d1,
title = "Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation",
abstract = "To address whether mitochondrial biogenesis is essential for skeletal myogenesis, C2C12 myogenesis was investigated after knockdown of NADH dehydrogenase (ubiquintone) flavoprotein 1 (NDUFV1), which is an oxidative phosphorylation complex I subunit that is the first subunit to accept electrons from NADH. The NDUFVI knockdown enhanced C2C12 myogenesis by decreasing the NAD+/NADH ratio and subsequently inactivating SIRT1 and SIRT1 activators (pyruvate, SRT1720, and resveratrol) abolished the NDUFV1 knockdown-induced myogenesis enhancement. However, the insulin-elicited activation of insulin receptor β (IRβ) and insulin receptor substrate-1 (IRS-1) was reduced with elevated levels of protein-tyrosine phosphatase 1B after NDUFV1 knockdown in C2C12 myotubes. The NDUFV1 knockdown-induced blockage of insulin signaling was released by protein-tyrosine phosphatase 1B knockdown in C2C12 myotubes, and we found that NDUFV1 or SIRT1 knockdown did not affect mitochondria biogenesis during C2C12 myogenesis. Based on these data, we can conclude that complex I dysfunction-induced SIRT1 inactivation leads to myogenesis enhancement but blocks insulin signaling without affecting mitochondria biogenesis.",
author = "Jin Hong and Kim, {Bong Woo} and Choo, {Hyo Jung} and Park, {Jung Jin} and Yi, {Jae Sung} and Yu, {Dong Min} and Hyun Lee and Yoon, {Gye Soon} and Lee, {Jae Seon} and Young-Gyu Ko",
year = "2014",
month = "1",
day = "1",
doi = "10.1074/jbc.M114.560078",
language = "English",
volume = "289",
pages = "20012--20025",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "29",

}

TY - JOUR

T1 - Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation

AU - Hong, Jin

AU - Kim, Bong Woo

AU - Choo, Hyo Jung

AU - Park, Jung Jin

AU - Yi, Jae Sung

AU - Yu, Dong Min

AU - Lee, Hyun

AU - Yoon, Gye Soon

AU - Lee, Jae Seon

AU - Ko, Young-Gyu

PY - 2014/1/1

Y1 - 2014/1/1

N2 - To address whether mitochondrial biogenesis is essential for skeletal myogenesis, C2C12 myogenesis was investigated after knockdown of NADH dehydrogenase (ubiquintone) flavoprotein 1 (NDUFV1), which is an oxidative phosphorylation complex I subunit that is the first subunit to accept electrons from NADH. The NDUFVI knockdown enhanced C2C12 myogenesis by decreasing the NAD+/NADH ratio and subsequently inactivating SIRT1 and SIRT1 activators (pyruvate, SRT1720, and resveratrol) abolished the NDUFV1 knockdown-induced myogenesis enhancement. However, the insulin-elicited activation of insulin receptor β (IRβ) and insulin receptor substrate-1 (IRS-1) was reduced with elevated levels of protein-tyrosine phosphatase 1B after NDUFV1 knockdown in C2C12 myotubes. The NDUFV1 knockdown-induced blockage of insulin signaling was released by protein-tyrosine phosphatase 1B knockdown in C2C12 myotubes, and we found that NDUFV1 or SIRT1 knockdown did not affect mitochondria biogenesis during C2C12 myogenesis. Based on these data, we can conclude that complex I dysfunction-induced SIRT1 inactivation leads to myogenesis enhancement but blocks insulin signaling without affecting mitochondria biogenesis.

AB - To address whether mitochondrial biogenesis is essential for skeletal myogenesis, C2C12 myogenesis was investigated after knockdown of NADH dehydrogenase (ubiquintone) flavoprotein 1 (NDUFV1), which is an oxidative phosphorylation complex I subunit that is the first subunit to accept electrons from NADH. The NDUFVI knockdown enhanced C2C12 myogenesis by decreasing the NAD+/NADH ratio and subsequently inactivating SIRT1 and SIRT1 activators (pyruvate, SRT1720, and resveratrol) abolished the NDUFV1 knockdown-induced myogenesis enhancement. However, the insulin-elicited activation of insulin receptor β (IRβ) and insulin receptor substrate-1 (IRS-1) was reduced with elevated levels of protein-tyrosine phosphatase 1B after NDUFV1 knockdown in C2C12 myotubes. The NDUFV1 knockdown-induced blockage of insulin signaling was released by protein-tyrosine phosphatase 1B knockdown in C2C12 myotubes, and we found that NDUFV1 or SIRT1 knockdown did not affect mitochondria biogenesis during C2C12 myogenesis. Based on these data, we can conclude that complex I dysfunction-induced SIRT1 inactivation leads to myogenesis enhancement but blocks insulin signaling without affecting mitochondria biogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84904479727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904479727&partnerID=8YFLogxK

U2 - 10.1074/jbc.M114.560078

DO - 10.1074/jbc.M114.560078

M3 - Article

C2 - 24895128

AN - SCOPUS:84904479727

VL - 289

SP - 20012

EP - 20025

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 29

ER -