A control center for mitochondrial navigation in neurons

我们正在试图了解控制人口流动的调控机制 细胞中的线粒体。一种蛋白质复合体，包括米尔顿、米罗和运动蛋白-1重链 链(KHC)是神经元线粒体运输所必需的。米罗居住在中央枢纽， 允许多种细胞信号来控制线粒体的运动。这些信号包括 吞噬有丝分裂、钙、缺氧和营养可获得性等。此外，与 这一提议，我们已经取得了令人振奋的初步结果，证明了一种新颖的 跨越线粒体外膜和内膜的机械--线粒体 膜间隙桥接(MIB)复合体，稳定MIRO并调节线粒体 能动性。这一新发现和我们过去的工作在十字路口提出了一个紧迫的问题 基础细胞生物学和神经生物学：这些离散的微途径是如何 在功能上协调或收敛于线粒体的完整性，以响应各种刺激 还有压力呢？在这个项目中，我们用经典的细胞生物学和 神经生物学方法与一种强大的遗传工具(果蝇)相结合 验证。目的1：剖析MIB-Miro复合体的功能意义。目标2： 以确定MIRO与其结合伙伴相互作用的性质。目标3：探索 米罗的监管信号和机制之间的相互作用。

We are seeking to understand the regulatory mechanisms that control the movements of mitochondria in cells. A protein complex that includes milton, Miro, and the kinesin-1 heavy chain (KHC) is essential for mitochondrial transport in neurons. Miro resides at the central hub to allow multiple cellular signals to control mitochondrial motility. These signals include mitophagy, calcium, hypoxia, and nutrient availability etc. Additionally, and most relevant to this proposal, we have obtained exciting preliminary results demonstrating that a novel machinery spanning both the mitochondrial outer and inner membranes–the mitochondrial intermembrane space bridging (MIB) complex, stabilizes Miro and regulates mitochondrial motility. This new discovery and our past work raise a burning question at the intersection of fundamental cell biology and neurobiology: How do these discrete Miro-pathways functionally coordinate or converge on mitochondrial integrity in response to various stimuli and stresses? In this project we are probing these questions using classical cell biological and neurobiological approaches combined with a powerful genetic tool (fruit flies) for functional validation. Aim 1: To dissect the functional significance of the MIB-Miro complex. Aim 2: To determine the nature of Miro interaction with its binding partners. Aim 3: To explore the interplay of the regulatory signals and machineries of Miro.