SNARE-dependent mitochondria-lysosome contacts regulate glial mitochondrial dynamics and dopaminergic neuron survival

Mitochondria are dynamic organelles that undergo fission and fusion, enabling swift structural modification to adapt cellular needs. Disturbances in mitochondrial dynamics, frequently defects ascribed to neurons, have been associated with pathological contexts such as neurodegeneration in Parkinson’s disease. Nonetheless, the mechanism of glial mitochondrial dynamics contributing to neurodegeneration remains unclear. Here we present evidence that the Drosophila R-SNARE VAMP7 regulates glial mitochondrial dynamics and dopaminergic neuron survival via modulating the dynamic of mitochondria-lysosome contact, which determines the mitochondrial fission site. Independent of its characterized role in autophagosome-lysosome fusion, glial VAMP7 depletion causes mitochondrial elongation and dysfunction, increased ROS levels, and production of lipid droplets. These conferred changes in glia in turn affects nearby dopaminergic neuron survival. Glial VAMP7 genetically interacts with the mitochondrial fission/fusion factors Drp1 and Marf1 and controls glial mitochondrial dynamics via regulating the frequency and duration of mitochondria-lysosome contact. Our findings indicate that SNARE proteins, although not direct mediators on mitochondrial fusion, provide spatial cues to modulate glial mitochondrial fission via organelle contacts, impacting on neuron survival in a non-cell-autonomous manner. ### Competing Interest Statement The authors have declared no competing interest.