Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells
Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells
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DOI：
10.1016/s0378-1119(01)00809-5
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发表时间：
2002-03-06
期刊：
影响因子：
3.5
通讯作者：
Scarpulla, RC
中科院分区：
文献类型：
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作者：
Scarpulla, RC
线粒体的生物发生和功能依赖于核基因的调控表达。最近的证据表明，转录激活因子和辅激活因子都是线粒体维持和增殖的重要介质。包括NRF-1、NRF-2、Sp1、YY 1、CREB和MEF-2/E-box因子等在内的几种序列特异性激活剂与呼吸链表达有关。值得注意的是，NRF-1、NRF-2和Sp1的识别位点对于编码呼吸、亚基、线粒体转录和复制因子以及某些血红素生物合成酶和蛋白质输入机制的组分的大多数核基因是共同的。此外，遗传学证据支持NRF-1在胚胎发育过程中维持mtDNA的作用。尽管有这些进展，多个转录因子整合到线粒体生物发生程序中的方法仍然是一个悬而未决的问题。随着转录辅激活因子PGC-1的发现，人们对这个问题有了新的认识。这种辅因子在棕色脂肪中是冷诱导的，并与多种转录因子相互作用以协调适应性产热的程序。作为该计划的一部分，PGC-1可以部分通过与NRF-1的直接相互作用上调线粒体生物发生所需的核基因。PGC-1的异位表达诱导呼吸亚基mRNA的表达，并导致培养细胞和转基因小鼠中的线粒体增殖。最近，PRC被表征为与PGC-1具有某些结构相似性的新型共激活剂，包括激活结构域、RS结构域和RNA识别基序。然而，与PGC-1不同，PRC在产热过程中不被显著诱导，而是在PGC-1不表达的条件下在培养细胞中被细胞周期调节。PRC具有与PGC-1非常相似的转录特异性，特别是在其与NRF-1的相互作用和NRF-1靶基因的激活方面。这些受调节的辅激活因子可以提供一种手段，用于在不同生理条件下将序列特异性激活因子整合到线粒体的生物发生和功能中。(C)2002 Elsevier Science B. V.保留所有权利。
The biogenesis and function of mitochondria rely upon the regulated expression of nuclear genes. Recent evidence points to both transcriptional activators and coactivators as important mediators of mitochondrial maintenance and proliferation. Several sequence-specific activators including NRF-1, NRF-2, Sp1, YY1, CREB and MEF-2/E-box factors, among others, have been implicated in respiratory chain expression. Notably, recognition sites for NRF-1, NRF-2 and Sp1 are common to most nuclear genes encoding respiratory, subunits, mitochondrial transcription and replication factors, as well as certain heme biosynthetic enzymes and components of the protein import machinery. Moreover, genetic evidence supports a role for NRF-1 in the maintenance of mtDNA during embryonic development. Despite these advances, the means by which multiple transcription factors are integrated into a program of mitochondrial biogenesis remains an open question. New insight into this problem came with the discovery of the transcriptional coactivator, PGC-1. This cofactor is cold inducible in brown fat and interacts with multiple transcription factors to orchestrate a program of adaptive thermogenesis. As part of this program, PGC-1 can up-regulate nuclear genes that are required for mitochondrial biogenesis in part through a direct interaction with NRF-1. Ectopic expression of PGC-1 induces the expression of respiratory subunit mRNAs and leads to mitochondrial proliferation in both cultured cells and transgenic mice. More recently, PRC was characterized as a novel coactivator that shares certain structural similarities with PGC-1 including an activation domain, an RS domain and an RNA recognition motif. However, unlike PGC-1, PRC is not induced significantly during thermogenesis but rather is cell-cycle regulated in cultured cells under conditions where PGC-1 is not expressed. PRC has a transcriptional specificity that is very similar to PGC-1, especially in its interaction with NRF-1 and in the activation of NRF-1 target genes. These regulated coactivators may provide a means for integrating sequence-specific activators in the biogenesis and function of mitochondria under diverse physiological conditions. (C) 2002 Elsevier Science B.V. All rights reserved.