The unresolved role of mitochondrial DNA in Parkinson's disease

An overview of published studies, their limitations, and future prospects

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

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Article number104495
JournalNeurochemistry International
Volume129
DOIs
StatePublished - Oct 1 2019

Fingerprint

Mitochondrial DNA
Parkinson Disease
Mitochondria
Adenosine Triphosphate
Mitochondrial Genome
Dopaminergic Neurons
Oxidative Phosphorylation
Point Mutation
Neurodegenerative Diseases
Homeostasis
Genome
Neurons
Research

Keywords

  • Homoplasmic mtDNA variation
  • Mitochondrial DNA
  • Mitochondrial haplogroups
  • mtDNA depletion
  • Parkinson's disease
  • Somatic mtDNA variation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Müller-Nedebock, A. C., Brennan, R. R., Venter, M., Pienaar, I. S., van der Westhuizen, F. H., Elson, J. L., ... Bardien, S. (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]. https://doi.org/10.1016/j.neuint.2019.104495

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; Bardien, Soraya.

In: Neurochemistry International, Vol. 129, 104495, 01.10.2019.

Research output: Contribution to journalReview article

Müller-Nedebock, Amica C. ; Brennan, Rebecca R. ; Venter, Marianne ; Pienaar, Ilse S. ; van der Westhuizen, Francois H. ; Elson, Joanna L. ; Ross, Owen A ; Bardien, Soraya. / The unresolved role of mitochondrial DNA in Parkinson's disease : An overview of published studies, their limitations, and future prospects. In: Neurochemistry International. 2019 ; Vol. 129.
@article{b25df0541b6643f7ba91bdfec51ae293,
title = "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.",
keywords = "Homoplasmic mtDNA variation, Mitochondrial DNA, Mitochondrial haplogroups, mtDNA depletion, Parkinson's disease, Somatic mtDNA variation",
author = "M{\"u}ller-Nedebock, {Amica C.} and Brennan, {Rebecca R.} and Marianne Venter and Pienaar, {Ilse S.} and {van der Westhuizen}, {Francois H.} and Elson, {Joanna L.} and Ross, {Owen A} and Soraya Bardien",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.neuint.2019.104495",
language = "English (US)",
volume = "129",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - The unresolved role of mitochondrial DNA in Parkinson's disease

T2 - An overview of published studies, their limitations, and future prospects

AU - Müller-Nedebock, Amica C.

AU - Brennan, Rebecca R.

AU - Venter, Marianne

AU - Pienaar, Ilse S.

AU - van der Westhuizen, Francois H.

AU - Elson, Joanna L.

AU - Ross, Owen A

AU - Bardien, Soraya

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - Homoplasmic mtDNA variation

KW - Mitochondrial DNA

KW - Mitochondrial haplogroups

KW - mtDNA depletion

KW - Parkinson's disease

KW - Somatic mtDNA variation

UR - http://www.scopus.com/inward/record.url?scp=85068079373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068079373&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2019.104495

DO - 10.1016/j.neuint.2019.104495

M3 - Review article

VL - 129

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

M1 - 104495

ER -