scholarly journals Do Somatic Mitochondrial DNA Mutations Contribute to Parkinson's Disease?

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Joanne Clark ◽  
Ying Dai ◽  
David K. Simon
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Point Mutations ◽  
Premature Aging ◽  
Mtdna Mutations ◽  
Dna Mutations ◽  
Mitochondrial Dna Polymerase ◽  
Mitochondrial Defect

A great deal of evidence supports a role for mitochondrial dysfunction in the pathogenesis of Parkinson's disease (PD), although the origin of the mitochondrial dysfunction in PD remains unclear. Expression of mitochondrial DNA (mtDNA) from PD patients in “cybrid” cell lines recapitulates the mitochondrial defect, implicating a role for mtDNA mutations, but the specific mutations responsible for the mitochondrial dysfunction in PD have been difficult to identify. Somatic mtDNA point mutations and deletions accumulate with age and reach high levels in substantia nigra (SN) neurons. Mutations in mitochondrial DNA polymeraseγ(POLG) that lead to the accumulation of mtDNA mutations are associated with a premature aging phenotype in “mutator” mice, although overt parkinsonism has not been reported in these mice, and with parkinsonism in humans. Together these data support, but do not yet prove, the hypothesis that the accumulation of somatic mtDNA mutations in SN neurons contribute to the pathogenesis of PD.

scholarly journals Mitochondrial Dysfunction in Parkinson’s Disease: Focus on Mitochondrial DNA

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 591
Author(s):  
Olga Buneeva ◽  
Valerii Fedchenko ◽  
Arthur Kopylov ◽  
Alexei Medvedev
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Nuclear Dna ◽  
Good Evidence ◽  
Inner Mitochondrial Membrane ◽  
Mtdna Mutations ◽  
Increased Risk ◽  
Mtdna Replication

Mitochondria, the energy stations of the cell, are the only extranuclear organelles, containing their own (mitochondrial) DNA (mtDNA) and the protein synthesizing machinery. The location of mtDNA in close proximity to the oxidative phosphorylation system of the inner mitochondrial membrane, the main source of reactive oxygen species (ROS), is an important factor responsible for its much higher mutation rate than nuclear DNA. Being more vulnerable to damage than nuclear DNA, mtDNA accumulates mutations, crucial for the development of mitochondrial dysfunction playing a key role in the pathogenesis of various diseases. Good evidence exists that some mtDNA mutations are associated with increased risk of Parkinson’s disease (PD), the movement disorder resulted from the degenerative loss of dopaminergic neurons of substantia nigra. Although their direct impact on mitochondrial function/dysfunction needs further investigation, results of various studies performed using cells isolated from PD patients or their mitochondria (cybrids) suggest their functional importance. Studies involving mtDNA mutator mice also demonstrated the importance of mtDNA deletions, which could also originate from abnormalities induced by mutations in nuclear encoded proteins needed for mtDNA replication (e.g., polymerase γ). However, proteomic studies revealed only a few mitochondrial proteins encoded by mtDNA which were downregulated in various PD models. This suggests nuclear suppression of the mitochondrial defects, which obviously involve cross-talk between nuclear and mitochondrial genomes for maintenance of mitochondrial functioning.

Novel mitochondrial DNA mutations in Parkinson's disease

2002 ◽  
Vol 109 (5-6) ◽  
pp. 721-729 ◽  
Author(s):  
G. Richter ◽  
A. Sonnenschein ◽  
T. Grünewald ◽  
H. Reichmann ◽  
B. Janetzky
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations

scholarly journals Pink1/Parkin link inflammation, mitochondrial stress, and neurodegeneration

2018 ◽  
Vol 217 (10) ◽  
pp. 3327-3329 ◽  
Author(s):  
Laura E. Newman ◽  
Gerald S. Shadel
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Stress ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations ◽  
Age Related ◽  
Sting Pathway

What causes inflammation in age-related neurodegenerative diseases remains a mystery. Sliter et al. (2018. Nature. https://doi.org/10.1038/s41586-018-0448-9) show that, when damaged mitochondria cannot be removed by mitophagy, stress from exercise or mitochondrial DNA mutations activates the proinflammatory cGAS–STING pathway that may contribute to Parkinson’s disease.

scholarly journals Mitochondrial DNA mutations in Parkinson's disease brain

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
David K. Simon ◽  
Joanne Clark Matott ◽  
Janaina Espinosa ◽  
Neeta A. Abraham
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations

scholarly journals Biocomplexity and Fractality in the Search of Biomarkers of Aging and Pathology: Mitochondrial DNA Profiling of Parkinson’s Disease

2020 ◽  
Vol 21 (5) ◽  
pp. 1758 ◽  
Author(s):  
Annamaria Zaia ◽  
Pierluigi Maponi ◽  
Martina Zannotti ◽  
Tiziana Casoli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Reference Sequence ◽  
Mtdna Sequences ◽  
Chaos Game Representation ◽  
Mtdna Mutations ◽  
Biomarkers Of Aging ◽  
Mtdna Sequence ◽  
Lacunarity Analysis

Increasing evidence implicates mitochondrial dysfunction in the etiology of Parkinson’s disease (PD). Mitochondrial DNA (mtDNA) mutations are considered a possible cause and this mechanism might be shared with the aging process and with other age-related neurodegenerative disorders such as Alzheimer’s disease (AD). We have recently proposed a computerized method for mutated mtDNA characterization able to discriminate between AD and aging. The present study deals with mtDNA mutation-based profiling of PD. Peripheral blood mtDNA sequences from late-onset PD patients and age-matched controls were analyzed and compared to the revised Cambridge Reference Sequence (rCRS). The chaos game representation (CGR) method, modified to visualize heteroplasmic mutations, was used to display fractal properties of mtDNA sequences and fractal lacunarity analysis was applied to quantitatively characterize PD based on mtDNA mutations. Parameter β, from the hyperbola model function of our lacunarity method, was statistically different between PD and control groups when comparing mtDNA sequence frames corresponding to GenBank np 5713-9713. Our original method, based on CGR and lacunarity analysis, represents a useful tool to analyze mtDNA mutations. Lacunarity parameter β is able to characterize individual mutation profile of mitochondrial genome and could represent a promising index to discriminate between PD and aging.

Variations of mitochondrial DNA polymerase γ in patients with Parkinson’s disease

2013 ◽  
Vol 260 (12) ◽  
pp. 3144-3149 ◽  
Author(s):  
S. Ylönen ◽  
P. Ylikotila ◽  
A. Siitonen ◽  
S. Finnilä ◽  
J. Autere ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Dna Polymerase ◽  
Mitochondrial Dna Polymerase ◽  
Dna Polymerase Γ

Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease

1998 ◽  
Vol 44 (2) ◽  
pp. 177-186 ◽  
Author(s):  
M. Gu ◽  
J. M. Cooper ◽  
J. W. Taanman ◽  
A. H. V. Schapira
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Defect

scholarly journals Mitochondrial Biogenesis, Telomere Length and Cellular Senescence in Parkinson’s Disease and Lewy Body Dementia

2021 ◽  
Author(s):  
Muhammad Asghar ◽  
Amani Odeh ◽  
Ahmad Jouni Fattahi ◽  
Alexandra Edward Henriksson ◽  
Aurelie Miglar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Telomere Length ◽  
Cellular Senescence ◽  
Mitochondrial Biogenesis ◽  
Copy Number ◽  
Cellular Aging ◽  
Mtdna Copy Number

Abstract Background Progressive age is the single major risk factor for neurodegenerative diseases. Cellular aging markers during the course of Parkinson’s disease (PD) have been implicated in previous studies, however majority of these studies have investigated the association of individual cellular aging hallmarks with PD but not jointly. Method Here, we have studied the association of PD with three aging hallmarks (telomere attrition, mitochondrial dysfunction, and cellular senescence) in blood and the brain tissue. Telomere length and mitochondrial DNA ( mtDNA ) copy number was assessed by qPCR, while mitochondrial function ( PGC-1α and PGC-1β ) and expression of cyclin-dependent kinase inhibitor 2A ( CDKN2A ), cellular senescence marker was measured by RT-qPCR. Results Our results show that patients diagnosed with PD had 20% lower mitochondrial DNA copy number but 26% longer telomeres in blood compared to controls. Moreover, telomere length in blood was positively correlated with medication (Levodopa Equivalent Daily Dose). Similar results were found in brain tissue, where patients with Parkinson’s disease (PD), Parkinson dementia (PDD) and Dementia with Lewy Bodies (DLB) showed (46-95%) depleted mtDNA copy number, but (7-9%) longer telomeres compared to controls. Furthermore, when compared to controls, patients had lower mitochondrial biogenesis ( PGC-1α and PGC-1β ) and higher load of cellular senescent cells in postmortem prefrontal cortex tissue, where DLB showing the highest effect among the patient groups. Conclusion Our results show that mitochondrial dysfunction and cellular senescence but not telomere shortening is associated with PD, PDD and DLB. Our findings suggest that mitochondrial copy number and function could be used as viable biomarker in blood as an early indicator for the risk of neurodegenerative diseases.

Sign in / Sign up

Export Citation Format

Share Document