Long time-lapse imaging reveals unique features of PARK2/Parkin-mediated mitophagy in mature cortical neurons |
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Authors: | Cai Qian Zakaria Hesham Mostafa Sheng Zu-Hang |
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Affiliation: | Synaptic Function Section; National Institute of Neurological Disorders and Stroke; National Institutes of Health; Bethesda, MD USA; Department of Cell Biology and Neuroscience; Rutgers University; Piscataway, NJ USA. |
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Abstract: | Proper degradation of aged and damaged mitochondria through mitophagy is essential to ensure mitochondrial integrity and function. Translocation of PARK2/Parkin onto damaged mitochondria induces mitophagy in many non-neuronal cell types. However, direct evidence showing PARK2-mediated mitophagy in mature neurons is controversial, leaving unanswered questions as to how, where, and by what time course PARK2-mediated mitophagy occurs in neurons following mitochondrial depolarization. We applied long time-lapse imaging in live mature cortical neurons to monitor the slow but dynamic and spatial PARK2 translocation onto damaged mitochondria and subsequent degradation through the autophagy-lysosomal pathway. In comparison with non-neuronal cells, our study reveals unique features of PARK2-mediated mitophagy in mature neurons, which will advance our understanding of pathogenesis of several major neurodegenerative diseases characterized by damaged mitochondria or a dysfunctional autophagy-lysosomal system. |
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Keywords: | mitochondria Parkin PARK2 lysosome autophagosome autophagy depolarization mitochondrial mobility neuronal mitophagy mitochondrial membrane potential mitochondrial quality control |
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