摘要
线粒体的能量代谢需要线粒体与细胞核的信息交流及两套基因组的协同表达。核基因与线粒体基因表达的协调依赖于转录因子,如核呼吸因子1(nuclear respiratory factor1,NSF1)、NRF2、线粒体转录因子A(mitochondrial transcription factor A,TFAM)、线粒体转录因子B(TFBM)、过氧化物体增殖活化受体α(peroxisome proliferator-activated receptor α,PPARα)、雌激素相关受体α(estrogen-related receptor α,ERRα)、特异性蛋白质1(specificity protein 1,Sp1)等,与过氧化物体增殖活化受体γ辅活化因子1(peroxisome proliferator-activated receptor γ coactivator-1,PGC-1)家族如PGC-1α、PGC-1β、PGC-1相关的辅活化因子(PGC-1-related coactivator,PRC)等之间的相互作用。首先,上述转录因子与呼吸链靶基因结合,作用于特定基因的转录、翻译和复制装置以及蛋白质输入和装配装置,通过转录因子之间的相互作用控制线粒体的功能状态。其次,在生理和病理条件下,线粒体存在由线粒体向细胞核的逆向信号传导通路。该通路涉及众多的信号分子,它们将感应信号传递到细胞核并影响核基因的表达。核基因表达的变化导致细胞代谢的重新调整以使细胞适应线粒体的功能状态。本文系统阐述了线粒体基因与核基因协同表达的机制,为我们理解线粒体能量代谢和基于信号传递的功能整合提供一个基础框架。
Mitochondrial biogenesis requires a coordination of expression of two genomes and therefore cross talk between the nucleus and mitochondria. Nucleomitochondrial coordination of gene expression depends on the interplay between transcription factors such as NRF1, NRF2, Tfam, TFBM, PPARα, ERRα, Sp1, and members of the PGC-1 family of regulated coactivators （PGC-1α, PGC-1β, and PRC, etc.）. Firstly, the transcription factors target genes that specify the respiratory chain, the mitochondrial transcription, translation and replication machinery, and protein import and assembly apparatus among others, which interactions among transcription factors control the mitochondrial functional status. Secondly, mitochondrial retrograde signaling is a pathway of communication from mitochondria to the nucleus under normal and pathophysiological conditions, which involves multiple factors that sense and transmit mitochondrial signals to effect changes in nuclear gene expression. These changes lead to a reconfiguration of metabolism to accommodate cells to adapt functional state in mitochondria. This review elucidates the mechanisms of coordination of gene expression between mitochondrial and nuclear genomes and provides a basic framework for understanding the integration of mitochondrial biogenesis and function with signaling events.
出处
《生命的化学》
CAS
CSCD
北大核心
2009年第6期803-811,共9页
Chemistry of Life
关键词
线粒体
转录因子
顺向调节
逆向调节
基因协同表达
mitochondria
transcription factor
anterograde regulation
retrograde regulation
coordination of gene expression
