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Accumulation of mitochondrial 7S DNA in idiopathic and LRRK2 associated Parkinson's disease.

Abstract：

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.

journal_name

EBioMedicine

journal_title

EBioMedicine

authors

Podlesniy P,Puigròs M,Serra N,Fernández-Santiago R,Ezquerra M,Tolosa E,Trullas R

doi

10.1016/j.ebiom.2019.09.015

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

554-567

issn

2352-3964

pii

S2352-3964(19)30613-9

journal_volume

48

pub_type

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