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

16 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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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  • Cite this

    Hong, J., Kim, B. W., Choo, H. J., Park, J. J., Yi, J. S., Yu, D. M., Lee, H., Yoon, G. S., Lee, J. S., & Ko, Y-G. (2014). Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation. Journal of Biological Chemistry, 289(29), 20012-20025. https://doi.org/10.1074/jbc.M114.560078