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

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

Science advances (2021-08-08)
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
ABSTRACT

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

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Tyrosine Hydroxylase Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Anti-Tyrosine Hydroxylase Antibody, clone LNC1, ascites fluid, clone LNC1, Chemicon®
Sigma-Aldrich
Uridine, ≥99%