Multiple pathways for mitophagy: A neurodegenerative conundrum for Parkinson's disease

NEUROSCIENCE LETTERS

卷:697

Review

Chu, Charleen T.^1,2,3 

[1] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh Inst Neurodegenerat Dis,McGowan Inst R, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh Inst Neurodegenerat Dis,McGowan Inst R, Pittsburgh, PA 15213 USA

[3] Univ Pittsburgh, Sch Med, Ctr Neurosci, Pittsburgh, PA 15213 USA

关键词: Mitochondria;    Autophagy;    Neurodegeneration;    Mitophagy;    Parkinson's disease dementia;    Dementia with Lewy bodies;    Parkinson's disease;   

DOI  :  10.1016/j.neulet.2018.04.004

来源: Elsevier

【 摘 要 】

It has been nearly a decade since the first landmark studies implicating familial recessive Parkinson's disease genes in the regulation of selective mitochondrial autophagy. The PTEN-induced kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin (encoded by the PARK2 gene) act together to mark depolarized mitochondria for degradation. There is now an extensive body of literature detailing key mediators and steps in this pathway, based mostly on work in transformed cell lines. However, the degree to which PINK1-triggered mitophagy contributes to mitochondrial quality control in the mammalian brain, and the extent to which its disruption contributes to Parkinson's disease pathogenesis remain uncertain. In recent years, it has become clear that there are multiple, potentially redundant, pathways of cargo specification for mitophagy. Important mitophagy-independent functions of PINK1 and Parkin are also emerging. This review summarizes key features of three major mitophagy cargo recognition systems: receptor-mediated, ubiquitin-mediated and cardiolipin-mediated. New animal models that may be useful for tracking the delivery of mitochondria into lysosomes in different neuronal populations will be highlighted. Combining these research tools with methods to selectively disrupt specific mitophagy pathways may lead to a better understanding of the potential role of mitophagy in modulating neuronal vulnerability in Parkinson's spectrum (PD/PDD/DLB) and other neurodegenerative diseases.

【 授权许可】

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