Abstract
Parkinson’s disease (PD), as one of the complex neurodegenerative disorders, affects millions of aged people. Although the precise pathogenesis remains mostly unknown, a significant number of studies have demonstrated that mitochondrial dysfunction acts as a major role in the pathogeny of PD. Both nuclear and mitochondrial DNA mutations can damage mitochondrial integrity. Especially, mutations in several genes that PD-linked have a closed association with mitochondrial dysfunction (e.g., Parkin, PINK1, DJ-1, alpha-synuclein, and LRRK2). Parkin, whose mutation causes autosomal-recessive juvenile parkinsonism, plays an essential role in mitochondrial quality control of mitochondrial biogenesis, mitochondrial dynamics, and mitophagy. Therefore, we summarized the advanced studies of Parkin’s role in mitochondrial quality control and hoped it could be studied further as a therapeutic target for PD.
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Abbreviations
- AMPK:
-
AMP-activated kinase
- ATP:
-
Adenosine triphosphate
- CCCP:
-
Carbonyl cyanide m-chlorophenylhydrazone
- DA:
-
Dopaminergic
- DUBs:
-
Deubiquitinating enzymes
- Drp1:
-
Dynamin-related protein 1
- ER:
-
Endoplasmic reticulum
- Fis1:
-
Fission 1
- MDV:
-
Mitochondrial-derived vesicle
- Mfn1:
-
Mitofusin1
- Mfn2:
-
Mitofusin2
- MID49 and MID51:
-
Mitochondrial dynamics of 49 and 51 kDa protein
- mtDNA:
-
Mitochondrial DNA
- OPA1:
-
Optic atrophy 1
- P-Ser65-Ub:
-
Phosphorylated S65 of Ub
- PD:
-
Parkinson’s disease
- ROS:
-
Reactive oxygen species
- SN:
-
Substantia nigra
- Ub:
-
Ubiquitin
- Ubl:
-
Ub-like
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This manuscript was supported by grants from the National Natural Science Foundation of China (No. 81473376), 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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XLW and YZ designed the structure of the manuscript. XLW drafted the manuscript. YZ, ZZW, YHY, STF, and NHC made the critical revisions and improvements for the manuscript. XLW, ZZW, and YZ finalized the paper.
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Wang, XL., Feng, ST., Wang, ZZ. et al. Parkin, an E3 Ubiquitin Ligase, Plays an Essential Role in Mitochondrial Quality Control in Parkinson’s Disease. Cell Mol Neurobiol 41, 1395–1411 (2021). https://doi.org/10.1007/s10571-020-00914-2
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DOI: https://doi.org/10.1007/s10571-020-00914-2