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A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson’s disease by highlighting the use of cybrid models
Mitochondria play important roles in the regulation of key cellular processes, including energy metabolism, oxidative stress response, and signaling towards cell death or survival, and are distinguished by carrying their own genome (mtDNA). Mitochondrial dysfunction has emerged as a prominent cellul...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072496/ https://www.ncbi.nlm.nih.gov/pubmed/35513611 http://dx.doi.org/10.1007/s00018-022-04304-3 |
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author | Lang, Martin Grünewald, Anne Pramstaller, Peter P. Hicks, Andrew A. Pichler, Irene |
author_facet | Lang, Martin Grünewald, Anne Pramstaller, Peter P. Hicks, Andrew A. Pichler, Irene |
author_sort | Lang, Martin |
collection | PubMed |
description | Mitochondria play important roles in the regulation of key cellular processes, including energy metabolism, oxidative stress response, and signaling towards cell death or survival, and are distinguished by carrying their own genome (mtDNA). Mitochondrial dysfunction has emerged as a prominent cellular mechanism involved in neurodegeneration, including Parkinson’s disease (PD), a neurodegenerative movement disorder, characterized by progressive loss of dopaminergic neurons and the occurrence of proteinaceous Lewy body inclusions. The contribution of mtDNA variants to PD pathogenesis has long been debated and is still not clearly answered. Cytoplasmic hybrid (cybrid) cell models provided evidence for a contribution of mtDNA variants to the PD phenotype. However, conclusive evidence of mtDNA mutations as genetic cause of PD is still lacking. Several models have shown a role of somatic, rather than inherited mtDNA variants in the impairment of mitochondrial function and neurodegeneration. Accordingly, several nuclear genes driving inherited forms of PD are linked to mtDNA quality control mechanisms, and idiopathic as well as familial PD tissues present increased mtDNA damage. In this review, we highlight the use of cybrids in this PD research field and summarize various aspects of how and to what extent mtDNA variants may contribute to the etiology of PD. |
format | Online Article Text |
id | pubmed-9072496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-90724962022-05-07 A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson’s disease by highlighting the use of cybrid models Lang, Martin Grünewald, Anne Pramstaller, Peter P. Hicks, Andrew A. Pichler, Irene Cell Mol Life Sci Review Mitochondria play important roles in the regulation of key cellular processes, including energy metabolism, oxidative stress response, and signaling towards cell death or survival, and are distinguished by carrying their own genome (mtDNA). Mitochondrial dysfunction has emerged as a prominent cellular mechanism involved in neurodegeneration, including Parkinson’s disease (PD), a neurodegenerative movement disorder, characterized by progressive loss of dopaminergic neurons and the occurrence of proteinaceous Lewy body inclusions. The contribution of mtDNA variants to PD pathogenesis has long been debated and is still not clearly answered. Cytoplasmic hybrid (cybrid) cell models provided evidence for a contribution of mtDNA variants to the PD phenotype. However, conclusive evidence of mtDNA mutations as genetic cause of PD is still lacking. Several models have shown a role of somatic, rather than inherited mtDNA variants in the impairment of mitochondrial function and neurodegeneration. Accordingly, several nuclear genes driving inherited forms of PD are linked to mtDNA quality control mechanisms, and idiopathic as well as familial PD tissues present increased mtDNA damage. In this review, we highlight the use of cybrids in this PD research field and summarize various aspects of how and to what extent mtDNA variants may contribute to the etiology of PD. Springer International Publishing 2022-05-05 2022 /pmc/articles/PMC9072496/ /pubmed/35513611 http://dx.doi.org/10.1007/s00018-022-04304-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Lang, Martin Grünewald, Anne Pramstaller, Peter P. Hicks, Andrew A. Pichler, Irene A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson’s disease by highlighting the use of cybrid models |
title | A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson’s disease by highlighting the use of cybrid models |
title_full | A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson’s disease by highlighting the use of cybrid models |
title_fullStr | A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson’s disease by highlighting the use of cybrid models |
title_full_unstemmed | A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson’s disease by highlighting the use of cybrid models |
title_short | A genome on shaky ground: exploring the impact of mitochondrial DNA integrity on Parkinson’s disease by highlighting the use of cybrid models |
title_sort | genome on shaky ground: exploring the impact of mitochondrial dna integrity on parkinson’s disease by highlighting the use of cybrid models |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9072496/ https://www.ncbi.nlm.nih.gov/pubmed/35513611 http://dx.doi.org/10.1007/s00018-022-04304-3 |
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