Wenz Tina, Luca Corneliu, Torraco Alessandra, Moraes Carlos T
Department of Neurology, University of Miami School of Medicine, Miami, FL 33136, USA.
Cell Metab. 2009 Jun;9(6):499-511. doi: 10.1016/j.cmet.2009.04.010.
Regulation of mitochondrial protein expression is crucial for the function of the oxidative phosphorylation (OXPHOS) system. Although the basal machinery for mitochondrial transcription is known, the regulatory mechanisms are not completely understood. Here, we characterized mTERF2, a mitochondria-localized homolog of the mitochondrial transcription termination factor mTERF1. We show that inactivation of mTERF2 in the mouse results in a myopathy and memory deficits associated with decreased levels of mitochondrial transcripts and imbalanced tRNA pool. These aberrations were associated with decreased steady-state levels of OXPHOS proteins causing a decrease in respiratory function. mTERF2 binds to the mtDNA promoter region, suggesting that it affects transcription initiation. In vitro interaction studies suggest that mtDNA mediates interactions between mTERF2 and mTERF3. Our results indicate that mTERF1, mTERF2, and mTERF3 regulate transcription by acting in the same site in the mtDNA promoter region and thereby mediate fine-tuning of mitochondrial transcription and hence OXPHOS function.
线粒体蛋白表达的调控对于氧化磷酸化（OXPHOS）系统的功能至关重要。尽管线粒体转录的基础机制已为人所知，但其调控机制尚未完全阐明。在此，我们对mTERF2进行了表征，它是线粒体转录终止因子mTERF1的线粒体定位同源物。我们发现，小鼠体内mTERF2的失活会导致肌病和记忆缺陷，这与线粒体转录本水平降低和tRNA库失衡有关。这些异常与OXPHOS蛋白的稳态水平降低相关，进而导致呼吸功能下降。mTERF2与线粒体DNA（mtDNA）启动子区域结合，表明它影响转录起始。体外相互作用研究表明，mtDNA介导mTERF2和mTERF3之间的相互作用。我们的结果表明，mTERF1、mTERF2和mTERF3通过作用于mtDNA启动子区域的同一位置来调节转录，从而介导线粒体转录的微调以及OXPHOS功能。
