Mitochondrial DNA Copy Number and D-loop Region Methylation in Carriers of Amyotrophic Lateral Sclerosis Gene Mutations

Overview

Journal Epigenomics

Specialty Genetics

Date 2018 Aug 9

PMID 30088417

Citations 41

Authors

Andrea Stoccoro

Lorena Mosca

Vittoria Carnicelli

Ugo Cavallari

Christian Lunetta

Alessandro Marocchi

Lucia Migliore

Fabio Coppede

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate mitochondrial DNA (mtDNA) copy number and D-loop region methylation in carriers of SOD1, TARDBP, FUS and C9orf72 mutations.

Methods: Investigations were performed in blood DNA from 114 individuals, including amyotrophic lateral sclerosis (ALS) patients, presymptomatic carriers and noncarrier family members.

Results: Increased mtDNA copy number (p = 0.0001) was observed in ALS patients, and particularly in those with SOD1 or C9orf72 mutations. SOD1 mutation carriers showed also a significant decrease in D-loop methylation levels (p = 0.003). An inverse correlation between D-loop methylation levels and the mtDNA copy number (p = 0.0005) was observed.

Conclusion: Demethylation of the D-loop region could represent a compensatory mechanism for mtDNA upregulation in carriers of ALS-linked SOD1 mutations.

Citing Articles

Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review.

Risi B, Imarisio A, Cuconato G, Padovani A, Valente E, Filosto M Eur J Neurol. 2025; 32(1):e70014.

PMID: 39831374 PMC: 11744304. DOI: 10.1111/ene.70014.

Exposure to Metals, Pesticides, and Air Pollutants: Focus on Resulting DNA Methylation Changes in Neurodegenerative Diseases.

Stoccoro A, Coppede F Biomolecules. 2024; 14(11).

PMID: 39595543 PMC: 11591912. DOI: 10.3390/biom14111366.

Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues.

Firdaus Z, Li X Int J Mol Sci. 2024; 25(21).

PMID: 39519209 PMC: 11546397. DOI: 10.3390/ijms252111658.

Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels.

Stoccoro A, Lari M, Migliore L, Coppede F Epigenomes. 2024; 8(4).

PMID: 39449362 PMC: 11503383. DOI: 10.3390/epigenomes8040038.

DNA methylation in amyotrophic lateral sclerosis: where do we stand and what is next?.

Coppede F Epigenomics. 2024; 16(17):1185-1196.

PMID: 39258797 PMC: 11457677. DOI: 10.1080/17501911.2024.2394380.