Despite the fundamental role of the mitochondrion in cellular energy production and its involvement in numerous human diseases, we still do not know the function of nearly 20% of the known mitochondrial proteins. My laboratory applies genomic, genetic, and biochemical tools to uncover the role of these uncharacterized proteins in the mitochondrial respiratory chain (MRC) biogenesis. MRC is the main site of cellular respiration and energy production and since the core components of the MRC are evolutionarily conserved, we reason that the assembly factors required to build the MRC should also be conserved. Therefore, we utilize multiple models systems, including yeast, zebrafish, and human cell lines, to determine the role of these conserved, uncharacterized mitochondrial proteins in bioenergetics, organismal development, and human disease pathogenesis.
Another poorly understood aspect of the mitochondrial energy metabolism is the role of phospholipids in maintaining the structural and functional integrity of the MRC. Although it is well known that the MRC is localized in the inner mitochondrial membrane, how the unique lipid milieu of the mitochondrial membrane influences the assembly and activity of the MRC is not fully understood. We have constructed yeast mutants with defined mitochondrial phospholipid compositions to systematically determine each lipid's role in MRC assembly and activity. Ultimately, defining the roles of mitochondrial proteins and phospholipids will allow us to develop better diagnostic and therapeutic options for human disorders resulting from mitochondrial dysfunction.