The biogenesis of the mitochondrial outer membrane – molecular mechanisms and involvement in human pathogenesis
The mitochondrial outer membrane (MOM) contains a diverse set of proteins including enzymes, components of the preprotein translocation machinery, pore-forming proteins, regulators of programmed cell death, and those that control the morphology of the organelle. All these proteins, like the vast majority of mitochondrial proteins, are nuclear-encoded, synthesized in the cytosol and harbor signals that are essential for their subsequent import into mitochondria. A functional mitochondrial protein import system is essential for cell viability.
Mitochondrial defects have been implicated in a wide variety of degenerative diseases, aging, and cancer. Hence, understanding the mechanism of mitochondrial biogenesis is of considerable importance to our ability to deal with mitochondria-related diseases. Furthermore, as many regulators of programmed cell death reside in the mitochondrial outer membrane, gaining an insight into their insertion process will improve our understanding of the apoptotic mechanism in general.
We investigate the molecular mechanisms by which the various mitochondrial outer membrane proteins are targeted to mitochondria, inserted into the outer membrane and assembled into functional complexes within the membrane. We study in addition the involvement of lipids in the biogenesis of the MOM. For our studies we use both yeast and mammalian tissue cultures as experimental systems.