Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function

生物 遗传学 TFAM公司 线粒体DNA 线粒体生物发生 细胞生物学 转录因子 抄写(语言学) 发起人 基因 线粒体 基因表达 语言学 哲学
作者
Richard C. Scarpulla
出处
期刊:Physiological Reviews [American Physiological Society]
卷期号:88 (2): 611-638 被引量:1485
标识
DOI:10.1152/physrev.00025.2007
摘要

Mitochondria contain their own genetic system and undergo a unique mode of cytoplasmic inheritance. Each organelle has multiple copies of a covalently closed circular DNA genome (mtDNA). The entire protein coding capacity of mtDNA is devoted to the synthesis of 13 essential subunits of the inner membrane complexes of the respiratory apparatus. Thus the majority of respiratory proteins and all of the other gene products necessary for the myriad mitochondrial functions are derived from nuclear genes. Transcription of mtDNA requires a small number of nucleus-encoded proteins including a single RNA polymerase (POLRMT), auxiliary factors necessary for promoter recognition (TFB1M, TFB2M) and activation (Tfam), and a termination factor (mTERF). This relatively simple system can account for the bidirectional transcription of mtDNA from divergent promoters and key termination events controlling the rRNA/mRNA ratio. Nucleomitochondrial interactions depend on the interplay between transcription factors (NRF-1, NRF-2, PPARα, ERRα, Sp1, and others) and members of the PGC-1 family of regulated coactivators (PGC-1α, PGC-1β, and PRC). 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. These factors are in turn activated directly or indirectly by PGC-1 family coactivators whose differential expression is controlled by an array of environmental signals including temperature, energy deprivation, and availability of nutrients and growth factors. These transcriptional paradigms provide a basic framework for understanding the integration of mitochondrial biogenesis and function with signaling events that dictate cell- and tissue-specific energetic properties.
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