Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
Environ Mol Mutagen. 2010 Jun;51(5):360-79. doi: 10.1002/em.20571.
Mammalian mitochondrial DNA encodes 37 essential genes required for ATP production via oxidative phosphorylation, instability or misregulation of which is associated with human diseases and aging. Other than the mtDNA-encoded RNA species (13 mRNAs, 12S and 16S rRNAs, and 22 tRNAs), the remaining factors needed for mitochondrial gene expression (i.e., transcription, RNA processing/modification, and translation), including a dedicated set of mitochondrial ribosomal proteins, are products of nuclear genes that are imported into the mitochondrial matrix. Herein, we inventory the human mitochondrial gene expression machinery, and, while doing so, we highlight specific associations of these regulatory factors with human disease. Major new breakthroughs have been made recently in this burgeoning area that set the stage for exciting future studies on the key outstanding issue of how mitochondrial gene expression is regulated differentially in vivo. This should promote a greater understanding of why mtDNA mutations and dysfunction cause the complex and tissue-specific pathology characteristic of mitochondrial disease states and how mitochondrial dysfunction contributes to more common human pathology and aging.
哺乳动物线粒体 DNA 编码了 37 种必需基因，这些基因通过氧化磷酸化产生 ATP，其不稳定性或失调与人类疾病和衰老有关。除了线粒体 DNA 编码的 RNA 种类（13 种 mRNA、12S 和 16S rRNAs 以及 22 种 tRNAs）外，线粒体基因表达所需的其他因素（即转录、RNA 加工/修饰和翻译），包括一组专门的线粒体核糖体蛋白，都是核基因的产物，这些基因被导入线粒体基质。本文中，我们列出了人类线粒体基因表达机制，并在此过程中强调了这些调节因子与人类疾病的特定关联。在这个迅速发展的领域，最近取得了重大的新突破，为研究线粒体基因表达在体内如何差异调控这一关键问题奠定了基础。这将促进我们更好地理解为什么 mtDNA 突变和功能障碍导致线粒体疾病状态下具有复杂和组织特异性的病理，以及线粒体功能障碍如何导致更常见的人类病理和衰老。
