Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons

Qian Cai, Hesham Mostafa Zakaria, Anthony Simone, Zu Hang Sheng

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondria are essential for neuronal survival and function. Proper degradation of aged and damaged mitochondria through mitophagy is a key cellular pathway for mitochondrial quality control. Recent studies have indicated that PINK1/Parkin-mediated pathways ensure mitochondrial integrity and function [1-8]. Translocation of Parkin to damaged mitochondria induces mitophagy in many nonneuronal cell types [9-16]. However, evidence showing Parkin translocation in primary neurons is controversial [9, 15, 17, 18], leaving unanswered questions as to how and where Parkin-mediated mitophagy occurs in neurons. Here, we report the unique process of dissipating mitochondrial Δψ m-induced and Parkin-mediated mitophagy in mature cortical neurons. Compared with nonneuronal cells, neuronal mitophagy is a much slower and compartmentally restricted process, coupled with reduced anterograde mitochondrial transport. Parkin-targeted mitochondria are accumulated in the somatodendritic regions where mature lysosomes are predominantly located. Time-lapse imaging shows dynamic formation and elimination of Parkin- and LC3-ring-like structures surrounding depolarized mitochondria through the autophagy-lysosomal pathway in the soma. Knocking down Parkin in neurons impairs the elimination of dysfunctional mitochondria. Thus, our study provides neuronal evidence for dynamic and spatial Parkin-mediated mitophagy, which will help us understand whether altered mitophagy contributes to pathogenesis of several major neurodegenerative diseases characterized by mitochondrial dysfunction and impaired transport.

Original languageEnglish (US)
Pages (from-to)545-552
Number of pages8
JournalCurrent Biology
Volume22
Issue number6
DOIs
StatePublished - Mar 20 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons'. Together they form a unique fingerprint.

Cite this