The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Spatial Parkin Translocation and Degradation of Damaged Mitochondria via Mitophagy in Live Cortical Neurons
Open accessAbstract
Summary 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 non-neuronal 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 Δψm-induced and Parkin-mediated mitophagy in mature cortical neurons. Compared with non-neuronal 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.
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Citations
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Metadata
- Authors
- Cai, Q., Zakaria, H. M., Simone, A., & Sheng, Z.-H.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 22
- Issue
- 6
- Pages
- 545-552
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2089180401
- Cited by
- 338
- References
- 11
- FWCI
- 18.31
- Type
- journal article
- Language
- en
- Open access
- bronze
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