Functionalizing the Unannotated Mitochondrial Proteome
Jared Rutter Howard Hughes Medical Institute and Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA Email: rutter@biochem.utah.edu
Mitochondria are dynamic and complex organelles that play a central role in all aspects of biology, including energy production, intermediary metabolism, and apoptosis. These broad cellular functions also place mitochondria as a central player in human health. Mitochondrial dysfunction is associated with a wide range of diseases, including cancer, type 2 diabetes, and most neurodegenerative disorders. As a result of these wide-ranging critical activities, many efforts have focused on identifying and characterizing the mitochondrial proteome, with over 1,000 proteins identified to date in mammals. Remarkably, however, roughly one-quarter of these proteins remain essentially uncharacterized. These include many proteins that are highly conserved throughout eukarya, a strong indication that they perform a fundamentally important function. The overall goal in this research is to provide a new understanding of the biochemical and cellular function of each conserved uncharacterized mitochondrial protein, determine how they contribute to normal mitochondrial activity and human disease. Our studies of a handful of these uncharacterized mitochondrial conserved proteins have revealed new roles for these proteins in critical aspects of mitochondrial function, including mitochondrial protein quality control, lipid synthesis and mitochondrial ETC complex and supercomplex assembly.
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