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.