Long time-lapse imaging reveals unique features of PARK2/Parkin-mediated mitophagy in mature cortical neurons

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.