Molecular Regulations of Mitochondrial Structure in Neuronal Homeostasis and Survival

众所周知，线粒体功能障碍表现为神经元功能障碍，这是由于高水平的线粒体功能障碍。 这些高度极化的细胞的能量需求，它们非凡的轴突长度和复杂性。 然而，神经元线粒体如何精确地控制嵴结构，以响应不断变化的... 不断变化的能量需求和氧化应激源以及这些调节如何影响神经元 多细胞生物体的功能和行为仍然难以捉摸。在初步研究中，我们 已经发现了MIC60在维持嵴结构方面的进化保守作用， 果蝇我们已经发现果蝇MIC 60（dMIC 60）的分子修饰，包括 磷酸化和氧化及其在维持嵴连接可塑性中的意义， 抗氧化应激。这些结果证明了dMIC 60及其 线粒体和神经元稳态的翻译后修饰。我们假设 包括磷酸化和氧化在内的dMIC 60的分子调节允许dMIC 60接受 细胞信号进行其功能，他们的失调可能导致神经元 功能障碍和退化。为了验证这个假设，我们将执行以下特定目标。 目的1：dMIC 60在神经元稳态中的作用。目的2：作为细胞的嵴结构 氧化损伤的原因。目的3：dMIC 60磷酸化和 氧化

Mitochondrial malfunction is well known to manifest as dysfunction of neurons, due to the high energetic demands of these highly polarized cells, their remarkable axonal length, and complexity. However, how neuronal mitochondria precisely control crista structure in response to ever- changing energy demands and oxidative stressors and how these regulations impact neuronal function and behavior in multicellular organisms remain elusive. In our Preliminary Studies, we have discovered an evolutionarily conserved role for MIC60 in maintaining crista structure in Drosophila. We have found molecular modifications of fly MIC60 (dMIC60) including phosphorylation and oxidation and their significance in maintaining crista junction plasticity and resisting oxidative stress. These results demonstrate the vital importance of dMIC60 and its posttranslational modifications for mitochondrial and neuronal homeostasis. We hypothesize that molecular regulations of dMIC60 including phosphorylation and oxidation allow dMIC60 to receive cellular signals to conduct its functions and that their misregulations could lead to neuronal dysfunction and degeneration. To test this hypothesis, we will perform the following Specific Aims. Aim 1: Roles for dMIC60 in neuronal homeostasis. Aim 2: Crista structure as a cellular cause for oxidative damage. Aim 3: Molecular mechanisms of dMIC60 phosphorylation and oxidation.