The unresolved role of mitochondrial DNA in Parkinson's disease: An overview of published studies, their limitations, and future prospects.

Abstract

Parkinson's disease (PD), a progressive neurodegenerative disorder, has long been associated with mitochondrial dysfunction in both sporadic and familial forms of the disease. Mitochondria are crucial for maintaining cellular homeostasis, and their dysfunction is detrimental to dopaminergic neurons. These neurons are highly dependent on mitochondrial adenosine triphosphate (ATP) and degenerate in PD. Mitochondria contain their own genomes (mtDNA). The role of mtDNA has been investigated in PD on the premise that it encodes vital components of the ATP-generating oxidative phosphorylation (OXPHOS) complexes and accumulates somatic variation with age. However, the association between mtDNA variation and PD remains controversial. Herein, we provide an overview of previously published studies on the role of inherited as well as somatic (acquired) mtDNA changes in PD including point mutations, deletions and depletion. We outline limitations of previous investigations and the difficulties associated with studying mtDNA, which have left its role unresolved in the context of PD. Lastly, we highlight the potential for further research in this field and provide suggestions for future studies. Overall, the mitochondrial genome is indispensable for proper cellular function and its contribution to PD requires further, more extensive investigation.

• Authors: Amica C Müller-Nedebock, Rebecca R Brennan, Marianne Venter, Ilse S Pienaar, Francois H van der Westhuizen, Joanna L Elson, Owen A Ross, Soraya Bardien
• Journal: Neurochemistry international (Neurochem Int) Vol. 129 Pg. 104495 (10 2019) ISSN: 1872-9754 [Electronic] England
• PMID: 31233840 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• DNA, Mitochondrial
• Mitochondrial Proteins
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Electron Transport Complex I

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)
• Confounding Factors, Epidemiologic
• DNA, Mitochondrial (genetics)
• Electron Transport Complex I (drug effects)
• Forecasting
• Gene Dosage
• Genes, Mitochondrial
• Genetic Predisposition to Disease
• Humans
• Hybrid Cells
• Maternal Inheritance
• Mitochondria (physiology)
• Mitochondrial Proteins (genetics, physiology)
• Mutation
• Oxidative Phosphorylation (drug effects)
• Parkinson Disease (epidemiology, genetics, physiopathology)
• Research Design
• Sequence Deletion