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

Müller-Nedebock, Amica C, Brennan, Rebecca R, Venter, Marianne, Pienaar, Ilse S, van der Westhuizen, Francois H, Elson, Joanna L, Ross, Owen A and Bardien, Soraya (2019) The unresolved role of mitochondrial DNA in Parkinson's disease: an overview of published studies, their limitations, and future prospects. Neurochemistry International, 129. 104495 1-14. ISSN 0197-0186

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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.

Item Type: Article
Keywords: Homoplasmic mtDNA variation; Mitochondrial DNA; Mitochondrial haplogroups; Parkinson's disease; Somatic mtDNA variation; mtDNA depletion
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Depositing User: Ilse Pienaar
Date Deposited: 15 Jul 2019 14:39
Last Modified: 15 Jul 2019 14:45
URI: http://sro.sussex.ac.uk/id/eprint/84909

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