Longitudinal tracking of neuronal mitochondria delineates PINK1/Parkin-dependent mechanisms of mitochondrial recycling and degradation

• DOI: 10.1126/sciadv.abf6580
• Publication Date: 2021-08-06T19:05:45Z
• Authors: Huihui Li; Zak Doric; Amandine Berthet; Danielle M. Jorgens; Mai K. Nguyen; Ivy Hsieh; Julia Margulis; Rebecca Fang; Jayanta Debnath; Hiromi Sesaki; Steve Finkbeiner; Eric Huang; Ken Nakamura
• Keywords: PINK1; MFN2; DNM1L

Altered mitochondrial quality control and dynamics may contribute to neurodegenerative diseases, including Parkinson's disease, but we understand little about these processes in neurons. We combined time-lapse microscopy correlative light electron track individual mitochondria neurons lacking the fission-promoting protein dynamin-related 1 (Drp1) delineate kinetics of PINK1-dependent pathways control. Depolarized recruit Parkin outer membrane, triggering autophagosome formation, rapid lysosomal fusion, redistribution. Unexpectedly, mitolysosomes are dynamic persist for hours. Some engulfed by healthy mitochondria, others deacidified before bursting. In other cases, is directly recruited matrix polarized mitochondria. Loss PINK1 blocks recruitment, causes LC3 accumulation within exacerbates Drp1KO toxicity dopamine These results define a distinct neuronal life cycle, revealing potential mechanisms recycling signaling relevant neurodegeneration.