Role of the Dynamin-Related GTPase, Mgm1p, in Mitochondrial Morphology

University Of California-Davis, Davis CA

Investigators

Abstract

Mitochondria are semiautonomous intracellular organelles evolutionarily derived from endosymbiont prokaryotes. They are the primary site in eukaryotic cells where the energy of chemical bonds is oxidatively converted to a metabolically useful form. Mitochondria are therefore often referred to as the "powerhouses" of the eukaryotic cell. Like chloroplasts, mitochondria are separated from the cytoplasm of the cell by a double membrane system. The long term goal of this research project is to understand in molecular detail how the structure of the double-membraned mitochondrion is controlled. This is a complex problem because the chemical and physical structures of the outer membrane and inner membrane are different. In contrast to the outer membrane, the mitochondrial inner membrane is typically convoluted. These convolutions, referred to as cristae, form as a consequence of the greater surface area of the inner membrane, and presumably function to increase the organelle's ability to make energy. Interestingly, despite their distinct structures, current data suggest that fission and fusion of both membranes occur in tandem and that the molecular components that regulate these events are exclusively associated with the outer membrane. However, the range of cristae morphologies observed in cells suggests that the inner membrane is dynamic and that dedicated mechanisms and components exist to maintain its unique structure and perhaps to coordinate the behaviors of the two membranes. Virtually nothing is known about the mechanisms that regulate inner membrane structure in mitochondria. In addition to the outer membrane-associated dynamin-related GTPase, Dnm1p, analyses from Dr. Nunnari's laboratory indicate that a second dynamin-related GTPase, Mgm1p, is localized to the mitochondrial inner membrane and that inner membrane structure in mgm1 mutant cells is specifically aberrant. Members of the dynamin GTPase family share the common function to regulate the structure of various biological membranes. Thus, based on these findings, Dr. Nunnari hypothesizes that Mgm1p regulates the structure of mitochondria in cells by functioning to remodel the inner membranes. The experiments that will be done with support from this award will test this hypothesis utilizing a combination of genetic, biochemical, and cytological techniques.