Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's diseaseResearch in context
Background: Both idiopathic and familial Parkinson's disease are associated with mitochondrial dysfunction. Mitochondria have their own mitochondrial DNA (mtDNA) and previous studies have reported that the release of mtDNA is a biomarker of Parkinson's disease. Methods: We have now investi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306139 |
| _version_ | 1818922908633792512 |
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| author | Petar Podlesniy Margalida Puigròs Núria Serra Rubén Fernández-Santiago Mario Ezquerra Eduardo Tolosa Ramon Trullas |
| author_facet | Petar Podlesniy Margalida Puigròs Núria Serra Rubén Fernández-Santiago Mario Ezquerra Eduardo Tolosa Ramon Trullas |
| author_sort | Petar Podlesniy |
| collection | DOAJ |
| description | Background: Both idiopathic and familial Parkinson's disease are associated with mitochondrial dysfunction. Mitochondria have their own mitochondrial DNA (mtDNA) and previous studies have reported that the release of mtDNA is a biomarker of Parkinson's disease. Methods: We have now investigated the relationship between mtDNA replication, transcription and release in fibroblasts from patients with idiopathic (iPD) and Leucine-rich repeat kinase 2G2019S -associated Parkinson's disease (LRRK2-PD), using Selfie-digital PCR, a method that allows absolute quantification of mtDNA genomes and transcripts. Findings: In comparison with healthy controls, we found that fibroblasts from patients with iPD or LRRK2-PD had a high amount of mitochondrial 7S DNA along with a low mtDNA replication rate that was associated with a reduction of cf-mtDNA release. Accumulation of 7S DNA in iPD and LRRK2-PD fibroblasts was related with an increase in H-strand mtDNA transcription. Interpretation: These results show that 7S DNA accumulation, low mtDNA replication, high H-strand transcription, and low mtDNA release compose a pattern of mtDNA dysfunction shared by both iPD and LRRK2-PD fibroblasts. Moreover, these results suggest that the deregulation of the genetic switch formed by 7SDNA that alternates between mtDNA replication and transcription is a fundamental pathophysiological mechanism in both idiopathic and monogenic Parkinson's disease. Keywords: mtDNA, Digital PCR, 7S DNA, Parkinson's disease, LRRK2, G2019S LRRK2 missense mutation |
| first_indexed | 2024-12-20T02:01:01Z |
| format | Article |
| id | doaj.art-11e26aeb99bd42769428bedd0a4c838f |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-20T02:01:01Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-11e26aeb99bd42769428bedd0a4c838f2022-12-21T19:57:19ZengElsevierEBioMedicine2352-39642019-10-0148554567Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's diseaseResearch in contextPetar Podlesniy0Margalida Puigròs1Núria Serra2Rubén Fernández-Santiago3Mario Ezquerra4Eduardo Tolosa5Ramon Trullas6Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain; Correspondence to: P. Podlesniy, Neurobiology Unit, IIBB/CSIC, CIBERNED, c/Rosselló 161, sexta planta, Barcelona 08036, Spain.Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Barcelona, SpainNeurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Barcelona, SpainNeurology Service, Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Barcelona, SpainNeurology Service, Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Barcelona, SpainNeurology Service, Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Barcelona, SpainNeurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain; Correspondence to: R. Trullas, Neurobiology Unit, IIBB/CSIC, IDIBAPS, CIBERNED, c/Rosselló 161, sexta planta, Barcelona 08036, Spain.Background: Both idiopathic and familial Parkinson's disease are associated with mitochondrial dysfunction. Mitochondria have their own mitochondrial DNA (mtDNA) and previous studies have reported that the release of mtDNA is a biomarker of Parkinson's disease. Methods: We have now investigated the relationship between mtDNA replication, transcription and release in fibroblasts from patients with idiopathic (iPD) and Leucine-rich repeat kinase 2G2019S -associated Parkinson's disease (LRRK2-PD), using Selfie-digital PCR, a method that allows absolute quantification of mtDNA genomes and transcripts. Findings: In comparison with healthy controls, we found that fibroblasts from patients with iPD or LRRK2-PD had a high amount of mitochondrial 7S DNA along with a low mtDNA replication rate that was associated with a reduction of cf-mtDNA release. Accumulation of 7S DNA in iPD and LRRK2-PD fibroblasts was related with an increase in H-strand mtDNA transcription. Interpretation: These results show that 7S DNA accumulation, low mtDNA replication, high H-strand transcription, and low mtDNA release compose a pattern of mtDNA dysfunction shared by both iPD and LRRK2-PD fibroblasts. Moreover, these results suggest that the deregulation of the genetic switch formed by 7SDNA that alternates between mtDNA replication and transcription is a fundamental pathophysiological mechanism in both idiopathic and monogenic Parkinson's disease. Keywords: mtDNA, Digital PCR, 7S DNA, Parkinson's disease, LRRK2, G2019S LRRK2 missense mutationhttp://www.sciencedirect.com/science/article/pii/S2352396419306139 |
| spellingShingle | Petar Podlesniy Margalida Puigròs Núria Serra Rubén Fernández-Santiago Mario Ezquerra Eduardo Tolosa Ramon Trullas Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's diseaseResearch in context EBioMedicine |
| title | Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's diseaseResearch in context |
| title_full | Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's diseaseResearch in context |
| title_fullStr | Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's diseaseResearch in context |
| title_full_unstemmed | Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's diseaseResearch in context |
| title_short | Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's diseaseResearch in context |
| title_sort | accumulation of mitochondrial 7s dna in idiopathic and lrrk2 associated parkinson s diseaseresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419306139 |
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