共 43 条
PGC-1β-Regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERRα
被引:135
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:
国家高技术研究发展计划(863计划);
中国国家自然科学基金;
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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