Discordant Monozygotic Parkinson Disease Twins: Role of Mitochondrial Integrity.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
23
07
2020
revised:
20
10
2020
accepted:
20
10
2020
pubmed:
24
10
2020
medline:
3
2
2021
entrez:
23
10
2020
Statut:
ppublish
Résumé
Even though genetic predisposition has proven to be an important element in Parkinson's disease (PD) etiology, monozygotic (MZ) twins with PD displayed a concordance rate of only about 20% despite their shared identical genetic background. We recruited 5 pairs of MZ twins discordant for idiopathic PD and established skin fibroblast cultures to investigate mitochondrial phenotypes in these cellular models against the background of a presumably identical genome. To test for genetic differences, we performed whole genome sequencing, deep mitochondrial DNA (mtDNA) sequencing, and tested for mitochondrial deletions by multiplex real-time polymerase chain reaction (PCR) in the fibroblast cultures. Further, the fibroblast cultures were tested for mitochondrial integrity by immunocytochemistry, immunoblotting, flow cytometry, and real-time PCR to quantify gene expression. Genome sequencing did not identify any genetic difference. We found decreased mitochondrial functionality with reduced cellular adenosine triphosphate (ATP) levels, altered mitochondrial morphology, elevated protein levels of superoxide dismutase 2 (SOD2), and increased levels of peroxisome proliferator-activated receptor-gamma coactivator-α (PPARGC1A) messenger RNA (mRNA) in skin fibroblast cultures from the affected compared to the unaffected twins. Further, there was a tendency for a higher number of somatic mtDNA variants among the affected twins. We demonstrate disease-related differences in mitochondrial integrity in the genetically identical twins. Of note, the clinical expression matches functional alterations of the mitochondria. ANN NEUROL 2021;89:158-164.
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Twin Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-164Informations de copyright
© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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