Abstract

In the post-genomic era, it is essential for our comprehension of basic biology and disease pathogenesis to define functions for the entire protein family. This endeavor has recently benefited from a process we refer to as “systems biochemistry” that helps overcome traditional barriers to the characterization of poorly understood proteins by combining modern large-scale and classical reductionist approaches. Because mitochondria have a well-defined proteome, comprehensive analyses of the entire mitochondrial system have been possible, positioning understudied proteins for productive mechanistic investigations. The identification of new mitochondrial proteins associated with diseases and long-sought “missing” proteins that perform essential functions has sped up thanks to systems biochemistry methods of the past few years. Together, these studies are providing a molecular framework for the study of mitochondrial pathogenesis and advancing our comprehension of mitochondrial functions.