Abstract
Parkinson’s disease (PD) is a severe neurodegenerative disorder caused by the progressive loss of dopaminergic neurons in the substantia nigra and affects millions of people. Currently, mitochondrial dysfunction is considered as a central role in the pathogenesis of both sporadic and familial forms of PD. Mitophagy, a process that selectively targets damaged or redundant mitochondria to the lysosome for elimination via the autophagy devices, is crucial in preserving mitochondrial health. So far, aberrant mitophagy has been observed in the postmortem of PD patients and genetic or toxin-induced models of PD. Except for mitochondrial dysfunction, mitophagy is involved in regulating several other PD-related pathological mechanisms as well, e.g., oxidative stress and calcium imbalance. So far, the mitophagy mechanisms induced by PD-related proteins, PINK1 and Parkin, have been studied widely, and several other PD-associated genes, e.g., DJ-1, LRRK2, and alpha-synuclein, have been discovered to participate in the regulation of mitophagy as well, which further strengthens the link between mitophagy and PD. Thus, in this view, we reviewed mitophagy pathways in belief and discussed the interactions between mitophagy and several PD’s pathological mechanisms and how PD-related genes modulate the mitophagy process.
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Abbreviations
- AD:
-
Alzheimer’s disease
- α-Syn:
-
Alpha-synuclein
- AMPK:
-
AMP-activated protein kinase
- ATP:
-
Adenosine triphosphate
- DA:
-
Dopaminergic
- Drp1:
-
Dynamin-related protein 1
- ER:
-
Endoplasmic reticulum
- LRRK2:
-
Leucine-rich repeat kinase 2
- MDVs:
-
Mitochondrial-derived vesicles
- Mfn1:
-
Mitofusion1
- Mfn2:
-
Mitofusion2
- MIM:
-
Mitochondrial inner membrane
- MOM:
-
Mitochondrial outer membrane
- mtDNA:
-
Mitochondrial DNA
- mTOR:
-
Mechanistic target of rapamycin
- OPTN:
-
Optineurin
- PD:
-
Parkinson’s disease
- PINK1:
-
PTEN-induced putative kinase 1
- ROS:
-
Reactive oxygen species
- SN:
-
Substantia nigra
- Ub:
-
Ubiquitin
- ULK1:
-
Unc-51-like kinase 1
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This manuscript was supported by Grants from the National Natural Science Foundation of China (Nos. 81473376, 81730096, and 81773924), Scientific Research In-depth Development Fund of Beijing University of Chinese Medicine (No. 2019-ZXFZJJ-074), CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-I2M-1-004), and the Drug Innovation Major Project (Nos. 2018ZX09711001-003-005 and 2018ZX09711001-009-013).
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YZ and ZZW designed the structure of the manuscript. XLW drafted the manuscript. STF, ZZW, YTW, YHY, ZPL, and NHC made the critical revisions and improvements for the manuscript. XLW and YZ finalized the paper. All authors approved the final version of the manuscript.
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Wang, XL., Feng, ST., Wang, YT. et al. Mitophagy, a Form of Selective Autophagy, Plays an Essential Role in Mitochondrial Dynamics of Parkinson’s Disease. Cell Mol Neurobiol 42, 1321–1339 (2022). https://doi.org/10.1007/s10571-021-01039-w
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DOI: https://doi.org/10.1007/s10571-021-01039-w