The distribution of mitochondria and other subcellular organelles during cell division is an essential process for the proliferation of eukaryotic cells, yet the mechanisms facilitating and controlling this process are unknown. The goal of this study is to analyze the molecular basis for the distribution of mitochondria during mitosis. A primary aim is to identify proteins and subcellular structures which mediate this transport process. A second goal is to characterize the specific roles of these components in intracellular mitochondrial movements. A long-term objective is to understand how the distribution of mitochondria and other organelles is coordinated with other essential events of the cell division cycle. Mechanisms that distribute mitochondria during mitosis will be studied using a combined biochemical and genetic approach. This approach will focus on a characterization of mutant cells of the yeast Saccharomyces cerevisiae which are defective in the segreation of mitochondria. These mutants, which were isolated previously, first will be analyzed morphologically to examine the effect of the mutations on cellular structures and events of the cell cycle. The mutants will be used next to clone genes that encode components which facilitate mitochondrial distribution, and information from gene analysis will guide the production of antisera against the gene products. These antibodies will be used to identify and localize the proteins, and to examine changes in cellular distribution of the proteins during the cell cycle. Binding studies will be employed to characterize the interaction of these MDM (mitochondrial distribution and morphology) proteins with mitochondria or other subcellular structures. In a latter stage on the investigation, additional components that interact with MDM proteins will be identified by both biochemical and genetic approaches, and the function of these new components will be examined. Additionally, proteins that mediate mitochondrial movement will be investigated in cells that divide by a different mitotic pattern, fission. These studies of mitochondiral movement should reveal new details of cellular organization and cell division, and provide a foundation for understanding the changes in cellular structure that accompany differentiation.
