| First Author | Cai Q | Year | 2012 |
| Journal | Curr Biol | Volume | 22 |
| Issue | 6 | Pages | 545-52 |
| PubMed ID | 22342752 | Mgi Jnum | J:182363 |
| Mgi Id | MGI:5315319 | Doi | 10.1016/j.cub.2012.02.005 |
| Citation | Cai Q, et al. (2012) Spatial Parkin Translocation and Degradation of Damaged Mitochondria via Mitophagy in Live Cortical Neurons. Curr Biol 22(6):545-52 |
| abstractText | 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 Deltapsi(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. |
