Authors: Qian Cai, Hesham Mostafa Zakaria and Zu-Hang Sheng

Qian Cai

Corresponding author: Caiq@ninds.nih.gov
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

Hesham Mostafa Zakaria

Synaptic Function Section; National Institute of Neurological Disorders and Stroke; National Institutes of Health; Bethesda, MD USA; Howard Hughes Medical Institute; National Institutes of Health Research Scholars Program; Bethesda, MD USA

Zu-Hang Sheng

Corresponding author: shengz@ninds.nih.gov
Synaptic Function Section; National Institute of Neurological Disorders and Stroke; National Institutes of Health; Bethesda, MD USA

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.

Autophagic Punctum to:
Q Cai, HM Zakaria, A Simone, Z-H Sheng. Spatial Parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons. Curr Biol 2012; 22: 545-52
PMID: 22342752 DOI: 10.1016/j.cub.2012.02.005

Received: March 19, 2012; Accepted: March 30, 2012; Published Online: June 1, 2012

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