PROJECT SUMMARY Lysosomes and mitochondria are essential organelles for maintaining neuronal homeostasis, and defects in their function and dynamics have previously been linked to multiple neurodegenerative diseases. In contrast, whether these two organelles undergo bidirectional crosstalk to contribute to disease pathogenesis is not well understood. Mitochondria-lysosome contact sites allow for this bidirectional regulation to modulate their network dynamics, motility and function. Thus, investigating the dynamics of mitochondria-lysosome contacts may provide new insights into their regulation and their roles in the etiology of neurodegenerative disorders. This research project uses advanced microscopy techniques to elucidate how defects in mitochondria-lysosome contact tethering dynamics and formation may contribute to neurodegenerative diseases. Importantly, these studies will help to highlight new cellular pathways contributing to neurodegeneration in different neurological disorders.