Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Annu Rev Genomics Hum Genet. 2010;11:25-44. doi: 10.1146/annurev-genom-082509-141720.
For nearly three decades, the sequence of the human mitochondrial genome (mtDNA) has provided a molecular framework for understanding maternally inherited diseases. However, the vast majority of human mitochondrial disorders are caused by nuclear genome defects, which is not surprising since the mtDNA encodes only 13 proteins. Advances in genomics, mass spectrometry, and computation have only recently made it possible to systematically identify the complement of over 1,000 proteins that comprise the mammalian mitochondrial proteome. Here, we review recent progress in characterizing the mitochondrial proteome and highlight insights into its complexity, tissue heterogeneity, evolutionary origins, and biochemical versatility. We then discuss how this proteome is being used to discover the genetic basis of respiratory chain disorders as well as to expand our definition of mitochondrial disease. Finally, we explore future prospects and challenges for using the mitochondrial proteome as a foundation for systems analysis of the organelle.
近三十年来，人类线粒体基因组（mtDNA）的序列为理解母系遗传疾病提供了分子框架。然而，绝大多数线粒体疾病是由核基因组缺陷引起的，这并不奇怪，因为 mtDNA 仅编码 13 种蛋白质。基因组学、质谱和计算的进步最近才使得系统地鉴定组成哺乳动物线粒体蛋白质组的 1000 多种蛋白质成为可能。在这里，我们回顾了近年来在描述线粒体蛋白质组方面的进展，并强调了对其复杂性、组织异质性、进化起源和生化多功能性的深入了解。然后，我们讨论了如何利用这种蛋白质组来发现呼吸链障碍的遗传基础，以及扩大对线粒体疾病的定义。最后，我们探讨了未来利用线粒体蛋白质组作为细胞器系统分析基础的前景和挑战。
