Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation [Signal Transduction]

June 3rd, 2014 by 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.

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 (CI) 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 (IR) and insulin receptor substrate-1 (IRS-1) was reduced with an elevated levels of protein tyrosine phosphatase 1B (PTP1B) after NDUFV1 knockdown in C2C12 myotubes. The NDUFV1 knockdown-induced blockage of insulin signaling was released by PTP1B 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 CI dysfunction-induced SIRT1 inactivation leads to myogenesis enhancement but blocks insulin signaling without affecting mitochondria biogenesis.
  • Posted in Journal of Biological Chemistry, Publications
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