PGC-1 beta-regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERR alpha.

Academic Article


  • The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) coactivator-1 beta (PGC-1 beta) is a well-established regulator of the beta-oxidation of fatty acids and the oxidative phosphorylation in mitochondria. However, the underlying mechanism of PGC-1 beta action remains elusive. This study reveals that PGC-1 beta is highly induced during myogenic differentiation and knockdown of endogenous PGC-1 beta by siRNA leads to a decrease in the expression of several mitochondria-related genes. In consistence, the over-expression of PGC-1 beta stimulates its target genes such as cytochrome c, ATP synthase beta and ALAS-1 by its interaction with two transcriptional factors, NRF-1 and ERR alpha. The deletion or mutation of NRF-1 and/or ERR alpha binding sites in target gene promoters attenuates their activation by PGC-1 beta. Moreover, inhibition of NRF-1 or ERR alpha by siRNA ablated the aforesaid function of PGC-1 beta and compromised the oxidative phosphorylation and mitochondrial biogenesis. Taken together, these results confirm the direct interaction of NRF-1 and ERR alpha with PGC-1 beta, and their participation in mitochondrial biogenesis and respiration.
  • Authors

    Published In

  • Mitochondrion  Journal
  • Keywords

  • Binding Sites, Carrier Proteins, Gene Deletion, Gene Expression, Gene Knockdown Techniques, Humans, Mitochondria, Muscle Fibers, Skeletal, Nuclear Respiratory Factor 1, Organelle Biogenesis, Promoter Regions, Genetic, Protein Interaction Mapping, RNA, Small Interfering, RNA-Binding Proteins, Receptors, Estrogen, Sequence Deletion
  • Digital Object Identifier (doi)

    Author List

  • Shao D; Liu Y; Liu X; Zhu L; Cui Y; Cui A; Qiao A; Kong X; Liu Y; Chen Q
  • Start Page

  • 516
  • End Page

  • 527
  • Volume

  • 10
  • Issue

  • 5