The Winge Lab is focused on cellular mitochondria. One major focus is the biogenesis of the mitochondrial electron transfer respiratory complexes II, III and IV within this organelle. Improper assembly of these complexes are evident in inherited and acquired diseases of patients with cardiomyopathy, hepatopathy, and neurological disorders. A key step in assembly of these complexes is the formation of their essential flavin, heme, and iron-sulfur centers, which are inserted by the involvement of assembly factor proteins.
Much of the current knowledge on the biogenesis of theses respiratory complexes was elucidated in Saccharomyces cerevisiae, and many of the known assembly factors are conserved in in humans. We seek to identify new proteins that mediate the biogenesis of succinate dehydrogenase, cytochrome c reductase and cytochrome c oxidase complexes and elucidate their mechanism of action. We use a combination of in vitro biochemical, in vivo cellular assays and genetic analyses in these pursuits. Specifically, we are studying how flavin and three iron-sulfur centers are formed in succinate dehydrogenase, how the heme and iron-sulfur centers are formed in cytochrome c reductase and the pathway of copper and heme a center formation in cytochrome oxidase. In these studies we are focused on known assembly factors as well as seeking novel factors that mediate formation of the redox centers.