Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun 20:14:885500.
doi: 10.3389/fnagi.2022.885500. eCollection 2022.

Mitochondrial Dysfunction in Parkinson's Disease: From Mechanistic Insights to Therapy

Xiao-Yan Gao  1   2 , Tuo Yang  1 , Ying Gu  1 , Xiao-Hong Sun  1   2
Affiliations
Review

Mitochondrial Dysfunction in Parkinson's Disease: From Mechanistic Insights to Therapy

Xiao-Yan Gao et al. Front Aging Neurosci. .

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders worldwide. There are currently no cures or preventative treatments for PD. Emerging evidence indicates that mitochondrial dysfunction is closely associated with pathogenesis of sporadic and familial PD. Because dopaminergic neurons have high energy demand, cells affected by PD exhibit mitochondrial dysfunction that promotes the disease-defining the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The mitochondrion has a particularly important role as the cellular "powerhouse" of dopaminergic neurons. Therefore, mitochondria have become a promising therapeutic target for PD treatments. This review aims to describe mitochondrial dysfunction in the pathology of PD, outline the genes associated with familial PD and the factors related to sporadic PD, summarize current knowledge on mitochondrial quality control in PD, and give an overview of therapeutic strategies for targeting mitochondria in neuroprotective interventions in PD.

Keywords: Parkinson’s disease; bioenergetics; mitochondrial dysfunction; mitochondrial quality control; therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mitochondrial dysfunction-related factors and mitochondrial quality control in Parkinson’s disease.
See this image and copyright information in PMC

References

    1. Aguirre J. D., Dunkerley K. M., Lam R., Rusal M., Shaw G. S. (2018). Impact of altered phosphorylation on loss of function of juvenile Parkinsonism-associated genetic variants of the E3 ligase parkin. J. Biol. Chem. 293 6337–6348. 10.1074/jbc.RA117.000605 - DOI - PMC - PubMed
    1. Aman Y., Ryan B., Torsetnes S. B., Knapskog A. B., Watne L. O., Mcewan W. A., et al. (2020). Enhancing mitophagy as a therapeutic approach for neurodegenerative diseases. Metabol. Bioenerg. Drivers Neurodegener. Dis. 155 169–202. 10.1016/bs.irn.2020.02.008 - DOI - PubMed
    1. Anand N., Holcom A., Broussalian M., Schmidt M., Chinta S. J., Lithgow G. J., et al. (2020). Dysregulated iron metabolism in C. elegans catp-6/Atp13A2 mutant impairs mitochondrial function. Neurobiol. Dis. 139:104786. 10.1016/j.nbd.2020.104786 - DOI - PMC - PubMed
    1. Ando M., Funayama M., Li Y., Kashihara K., Murakami Y., Ishizu N., et al. (2012). Vps35 mutation in Japanese patients with typical Parkinson’s disease. Mov. Disord. 27 1413–1417. 10.1002/mds.25145 - DOI - PubMed
    1. Angelova P. R., Choi M. L., Berezhnov A. V., Horrocks M. H., Hughes C. D., De S., et al. (2020). Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation. Cell Death Differ. 27 2781–2796. - PMC - PubMed