title: PGC-1 beta-regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERR alpha.
abstract: 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.affiliation: The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
authors.forename: Di
authors.initials: D
authors.lastname: Shao
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: Liuluan
authors.initials: L
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Anfang
authors.initials: A
authors.lastname: Cui
authors.forename: Aijun
authors.initials: A
authors.lastname: Qiao
authors.forename: Xingxing
authors.initials: X
authors.lastname: Kong
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Nishith
authors.initials: N
authors.lastname: Gupta
authors.forename: Fude
authors.initials: F
authors.lastname: Fang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism*; D001678:Organelle Biogenesis; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D002352:Carrier Proteins; D051266:Nuclear Respiratory Factor 1; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C495633:NRF1 protein, human; C455622:PPARGC1B protein, human