title: Long time-lapse imaging reveals unique features of PARK2/Parkin-mediated mitophagy in mature cortical neurons.
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.
authors: Synaptic Function Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. cai@biology.rutgers.edu
authors: Qian
authors: Q
authors: Cai
authors: Hesham Mostafa
authors: HM
authors: Zakaria
authors: Zu-Hang
authors: ZH
authors: Sheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000473:pathology*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D063306:Mitophagy; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D059008:Time-Lapse Imaging / Q000379:methods*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein