Mitochondrial Motility and Inheritance

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Mitochondrial inheritance is the process whereby mitochondria are transferred from mother to daughter cell during cell division. During inheritance in budding yeast, mitochondria are actively transferred to opposite poles of the cell. After transport, mitochondria are anchored to and retained at the poles until the end of the division cell cycle. The net effect of these motility and retention events is the equal distribution of the organelle between mother and daughter cells. The cytoskeletal track for movement of mitochondria, endosomes, secretory vesicles, mRNAs, and other cargos in yeast are actin cables, bundles of F-actin that run from pole to pole. We found that actin cables are moving tracks that undergo elongation-driven extension from the bud into the mother cell. This "retrograde flow" affects movement of mitochondria toward both poles. For retrograde movement, mitochondria bind to actin cables undergoing retrograde flow and use these cables as "conveyor belts" for transport toward the mother cell tip. Movement of mitochondria to the opposite pole requires reversible binding of the organelle to actin cables, and anterograde forces at the interface between mitochondria and actin cables. Several molecules contribute to this anterograde movement: 1) the mitochore mediates binding of mitochondria with actin cables, 2) the Arp2/3 complex generates anterograde forces at the organelle-actin cable interface, and 3) 2 Pumilio family proteins (Jsn1p and Puf3p) recruit Arp2/3 complex to mitochondria. Anchorage of mitochondria in the bud requires a type V myosin (Myo2p), and 2 Myo2p binding partners (Ypt11p a Ras-like G-protein, and Mmrlp). Our studies also revealed a novel regulatory system, that inhibits cytokinesis when mitochondrial inheritance is defective. This process is regulated by the mitotic exit network (MEN), a signal transduction pathway that coordinates chromosome segregation, exit from M-phase, and cytokinesis. Thus, we are now in a position to move from a description of mitochondrial motility during inheritance in budding yeast to understanding the molecular basis for this process and how mitochondrial inheritance is integrated into the cell cycle as a whole. We will study the interaction of Pumilio family proteins with mitochondria and the Arp2/3 complex, to more fully understand Arp2/3 complex targeting to mitochondria. We will study the role of Myo2p, Ypt11p, and Mmrlp in anchorage of mitochondria in the bud tip. Finally, we will study how mitochondrial inheritance is monitored and integrated with signal transduction by the MEN.