Mitophagy, a Form of Selective Autophagy, Plays an Essential Role in Mitochondrial Dynamics of Parkinson’s Disease

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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Fig. 1
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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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Acknowledgements

We thank everyone who contributed to this manuscript.

Funding

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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Correspondence to Zhen-Zhen Wang or Yi Zhang.

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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 (2021). https://doi.org/10.1007/s10571-021-01039-w

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Keywords

  • Parkinson’s disease
  • Mitochondrial function
  • Mitochondrial dynamics
  • Mitophagy
  • Mitochondrial quality control