Regulation of mitochondrial dynamics pathways in mammalian cells

项目摘要 线粒体的功能是由一个复杂的，相互交织的机制， 线粒体大体形态、细胞器运输、内膜和嵴形态， 相邻线粒体之间的通信和与其他细胞器的接触。这些过程 统称为线粒体动力学。我的总体目标是全面了解 控制线粒体动力学的机制以及线粒体转运与 线粒体和细胞生物学的其他方面。虽然线粒体转运的机制已经被 我们最近的进展表明，在神经元中， 线粒体到皮质细胞骨架支持板状伪足动力学，促进局灶性粘附的周转 复合并增加上皮细胞中随机细胞迁移的速度和距离。因为专业化 细胞类型对线粒体功能有独特的时空需求，一个基本问题是如何相似 是神经元和其他细胞类型之间线粒体运动的机制？在这里，我们将重点介绍 表征表达于细胞中的运输蛋白的替代同种型的功能和调节， 非神经元细胞。使这一情况更加复杂的是，我们有证据表明贩运活动具有多功能性， 非神经元细胞中的蛋白质。这些新的功能包括线粒体代谢和线粒体功能。 信号这就提出了一个重要的问题：这些多功能蛋白质是如何被如此单一或 在特定的时间和地点启用双重功能？总的来说，我的研究计划将导致 在非神经元细胞中线粒体运输和线粒体信号通路的调节方面的发现 细胞因为线粒体是维持细胞内稳态的关键细胞器， 功能障碍与神经和代谢疾病，癌症和衰老有关，我们的进展 有可能告知如何利用这些机制在医学上的实际应用。

PROJECT SUMMARY Mitochondria function is tightly regulated by a complex, intertwined machinery that dictates mitochondrial gross morphology, transport of organelles, inner membrane and cristae morphology, communication between adjacent mitochondria and contact with other organelles. These processes are collectively known as mitochondrial dynamics. My overall goal is to reach a comprehensive understanding on the mechanisms that govern mitochondrial dynamics and the interplay between mitochondrial transport with other aspects of mitochondrial and cellular biology. While the mechanisms of mitochondrial transport had been largely characterized in neurons, our recent advances showed that transport of energetically active mitochondria to the cortical cytoskeleton supports lamellipodia dynamics, fuels turnover of focal adhesion complexes and increases velocity and distance of random cell migration in epithelial cells. Because specialized cell types have unique spatiotemporal needs for mitochondria functions, a fundamental question is how similar are the mechanisms of mitochondrial movement between neurons and other cell types? Here we will focus on characterizing the function and regulation of alternative isoforms of trafficking proteins that are expressed in non-neuronal cells. Adding complexity to this picture, we have evidence of multifunctionality amongst trafficking proteins in non-neuronal cells. These novel functions include mitochondrial metabolism and mitochondrial signaling. This poses an important question: how are these multifunctional proteins regulated so single or double functions are enabled at a particular time and location? Overall, my research program will lead to discoveries on the regulation of mitochondrial trafficking and mitochondrial signaling pathways in non-neuronal cells. Because mitochondria are key organelles that maintain cellular homeostasis, and mitochondrial dysfunction are associated with neurological and metabolic diseases, cancer and aging, our advances have the potential to inform how to exploit these mechanisms for practical applications in medicine.