The distribution of mitochondria and other subcellular organelles during cell division is essential for the proliferation of eukaryotic cells, yet little is know of its molecular basis or control. The goal of this study is to identify and characterize molecular mechanisms facilitating mitochondrial division and distribution during mitotic growth. A primary aim is to identify proteins and subcellular structures which mediate these processes. A second goal is to characterize the specific roles of these components in intracellular mitochondrial movements. A long-term objective is to understand how organelle division and distribution is coordinated with other essential events of the cell division cycle. Components that mediate mitochondrial inheritance will be studied using a combined biochemical and genetic approach. This approach is based on the earlier isolation and analysis of mutant cells of the yeast Saccharomyces cerevisiae which display conditional defects in mitochondrial distribution and morphology (mdm mutants). Initial studies will focus on the products of the MDM9 and MDM10 genes which are required for mitochondrial inheritance. MDM9 also mediates nuclear inheritance, while MDM10 plays a role in mitochondrial division. The MDM9 MDM10 proteins will be identified through gene cloning and analysis, and localized in wild-type and mutant cells using immunological and microscopic techniques. The interaction of MDM9 and MDM10 with mitochondria and other cellular structures will be examined with binding studies in vitro. Isolation and analysis of new mutant alleles and extrageneic suppressors of mdm10 will allow an analysis of relationships between mitochondrial division and mitochondrial inheritance. A second aspect of this study is the isolation and characterization of additional mutants affecting mitochondrial distribution and morphology. New mutants will be analyzed morphologically and genetically, and new MDM proteins will be identified via gene cloning and analysis. In a third component of this investigation, a homolog of MDM1, a key protein required for both mitochondrial and nuclear inheritance, will be identified in the fission yeast, Schizosaccharomyces pombe. Structural and functional analysis of this protein will extend studies of mitochondrial inheritance to cells that divide by a different mitotic plan, fission. These studies of mitochondrial movement should reveal new details of cellular organization and cell division, and provide a foundation for understanding the changes in cellular structure and function associated with numerous disease states.
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