Professor Moira Glerum has developed a research program aimed at understanding the macromolecular assembly pathway for cytochrome oxidase (COX), the terminal electron acceptor in the mitochondrial respiratory chain. Using yeast as a model system, Professor Glerum's research has identified and characterized novel proteins involved in COX assembly. Since mutations in some of these proteins result in a spectrum of inherited diseases, her studies in yeast have improved our understanding of the molecular mechanisms underlying human mitochondrial disorders. Her current studies are geared towards understanding the relationship between copper provision/distribution and mitochondrial peroxide metabolism.
Research interests
Mitochondrial myopathies; mitochondrial biogenesis; assembly of cytochrome oxidase in yeast and humans.
Mitochondria are the "power plants" of our cells and generate almost all of the energy we need to live. The failure of these energy generators results in a wide variety of human diseases. In fact, defects in mitochondrial function may be the most common underlying cause of neurodegenerative disease! Mitochondria are created from proteins encoded in two different genomes - the nuclear and the mitochondrial. Our lab is studying the contributions of both of these genomes to neurodegenerative diseases and cancer. The nuclear genome encodes most of the proteins required for mitochondrial formation. One of the key enzymes found in mitochondria is cytochrome oxidase (COX), which consists of 13 subunits - 3 encoded in mtDNA and 10 encoded in the nucleus. However, there are also more than a dozen proteins involved in ensuring that COX is correctly assembled, all of which are also encoded in the nucleus. The COX assembly pathway is most often defective in human COX deficiencies, which are the most common of the mitochondrial respiratory chain disorders. These diseases usually present early in life and are almost always fatal. The COX assembly pathway is still only partially understood and we are using yeast as a model system for delineating this process. Our studies are furthering our understanding of how mutations in COX assembly genes result in fatal neurological disease. Microfluidic chip, or lab-on-a-chip, technologies have the potential to revolutionize both health care delivery and biomedical research. Given the ever-increasing list of disorders with a documented mitochondrial dysfunction, technologies that would enable us to investigate mitochondrial function at the level of a single cell would further our understanding of the contributions of this organelle to disease pathologies. In collaboration with the Backhouse lab in Electrical and Computer Engineering, we are therefore also developing microfluidic chip-based assays for use in studying mitochondrial disease.
