PGC-1β-Regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERRα

被引:132
作者
Shao, Di [2 ,3 ]
Liu, Yang [2 ,3 ]
Liu, Xiaojun [2 ,3 ]
Zhu, Liuluan [2 ,3 ]
Cui, Ying [2 ,3 ]
Cui, Anfang [2 ,3 ]
Qiao, Aijun [2 ,3 ]
Kong, Xingxing [2 ,3 ]
Liu, Yong [4 ]
Chen, Quan [4 ]
Gupta, Nishith [1 ]
Fang, Fude [2 ,3 ]
Chang, Yongsheng [2 ,3 ]
机构
[1] Humboldt Univ, Dept Mol Parasitol, D-10115 Berlin, Germany
[2] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China
[3] Peking Union Med Coll, Beijing 100005, Peoples R China
[4] Chinese Acad Sci, Inst Zool, Natl Key Lab Biomembrane & Membrane Biotechnol, Lab Apoptosis & Canc Biol, Beijing 100101, Peoples R China
基金
中国国家自然科学基金; 国家高技术研究发展计划(863计划);
关键词
PGC-1; beta; NRF-1; ERR alpha; Cytochrome c; Mitochondrial biogenesis; Energy metabolism; HUMAN SKELETAL-MUSCLE; RECEPTOR-ALPHA; ADAPTIVE THERMOGENESIS; INSULIN-RESISTANCE; OXIDATIVE-PHOSPHORYLATION; INDUCIBLE COACTIVATOR; ENERGY-METABOLISM; PGC-1; FAMILY; EXPRESSION; TRANSCRIPTION;
D O I
10.1016/j.mito.2010.05.012
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. (C) 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
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页码:516 / 527
页数:12
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