Mitochondrial Motility and Inheritance

线粒体运动和遗传

基本信息

批准号：
7912048
负责人：
Liza A Pon
金额：
$ 17.33万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-16 至 2011-06-30
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：线粒体遗传是在细胞分裂期间将线粒体从母细胞转移到子细胞的过程。在萌芽酵母中的遗传过程中，线粒体被积极转移到细胞的相对极。运输后，线粒体被锚定并保留在两极，直到分裂细胞周期结束。这些运动和保留事件的净效应是母细胞之间细胞器的相等分布。线粒体运动，内体，分泌囊泡，mRNA和其他酵母中的其他曲线的细胞骨架轨道是酵母肌动蛋白电缆，是从极点到极的F-肌动蛋白束。我们发现，肌动蛋白电缆正在移动从芽进入母细胞的延伸驱动延伸的轨道。这种“逆行流”会影响线粒体向两极的运动。为了逆行运动，线粒体与逆行流动的肌动蛋白电缆结合，并将这些电缆用作“输送带”，以向母细胞尖端运输。线粒体向相对极的运动需要细胞器与肌动蛋白电缆的可逆结合，以及线粒体和肌动蛋白电缆之间的界面处的顺行力。几个分子有助于这种顺行运动：1）线形介导线粒体与肌动蛋白电缆的结合，2）ARP2/3复合物在细胞器 - 肌动蛋白电缆界面和3）2 pumilio家族蛋白（JSN1P和PUF3P）招募ARP2/3复杂的ARP2/3复合物在细胞器 - 肌动蛋白电缆界面上产生顺行力。线粒体在芽中的锚固需要V型V肌球蛋白（MyO2p）和2个MyO2P结合伙伴（YPT11p a ras like g蛋白和MMRLP）。我们的研究还揭示了一种新型的调节系统，该系统会在线粒体遗传有缺陷时抑制细胞因子。该过程受丝分裂出口网络（MEN）的调节，这是一种信号转导途径，可协调染色体分离，从M期退出和细胞因子。因此，我们现在可以从萌芽酵母中遗传过程中的线粒体运动的描述转变为理解该过程的分子基础，以及如何将线粒体遗传整合到整个细胞周期中。我们将研究Pumilio家族蛋白与线粒体和ARP2/3复合物的相互作用，以更充分地了解ARP2/3复合物靶向线粒体。我们将研究Myo2p，YPT11p和MMRLP在芽尖中线粒体锚定中的作用。最后，我们将研究如何监测线粒体的遗传和与男性信号转导的整合。