线粒体及其与内质网相互作用的分子机制研究

线粒体功能的正常行使取决于其处于动态平衡的分裂和融合及其与其它细胞器的互作。近年来线粒体与内质网互作正在日益成为研究的一个热点，其具体调控机制仍有待进一步发掘。同时，人们长期以来对线粒体自身的分裂和融合事件之间的关联及关联规律仍然研究不足。我们近期的研究表明Mitofusin的裂殖酵母同源蛋白Fzo1不仅具有传统的线粒体融合功能，而且也参与调控线粒体分裂和调控内质网与线粒体的连接。这些发现提示Fzo1可能是线粒体融合分裂关联及线粒体与内质网互作的关键调控蛋白。为此，本研究将以Fzo1/MFN1/MFN2为主要切入点，以裂殖酵母为主要模式生物结合利用人类细胞系，通过综合应用高（超）分辨率活细胞共聚焦显微镜、酵母遗传学、生物化学等技术手段研究线粒体及其与内质网互作的分子机制。鉴于线粒体与肿瘤、神经退行性疾病、代谢紊乱等重大疾病息息相关，本研究将为理解相关疾病和发展干预策略奠定理论基础。

Mitochondria are highly dynamic within the cell constantly undergoing fission and fusion. The balance between fission and fusion ensures proper mitochondrial functions. In addition, proper mitochondrial functions require the interaction of mitochondria with other cellular organelles. Particularly, the interaction between mitochondria and the endoplasmic reticulum has become a focus of intense study. Our recent study on the yeast Mitofusin Fzo1 revealed that Fzo1 is required for proper mitochondria-ER interaction and for regulating the balance between mitochondrial fission and fusion. Based on these findings, we propose to investigate the mechanistic role of Fzo1/MFN1/MFN2 in regulating mitochondria-ER interaction and in regulating the balance of mitochondrial fission and fusion, using a combination of live-cell confocal microscopy, yeast genetics, and biochemistry approaches. As mitochondrial dysfunction has been associated with cancer, neurodegenerative, metabolic diseases, the findings from this work will pave the way for further clinical study and facilitate the development of intervention strategies.