Andrea Stoccoro1,2, Lorena Mosca3, Vittoria Carnicelli4, Ugo Cavallari3, Christian Lunetta5, Alessandro Marocchi3, Lucia Migliore1, Fabio Coppedè1. 1. Department of Translational Research & New Technologies in Medicine & Surgery, Medical Genetics Laboratory, University of Pisa, Pisa, Italy. 2. Doctoral School in Genetics Oncology & Clinical Medicine, Department of Medical Biotechnologies, University of Siena, Siena, Italy. 3. Medical Genetics Unit, Department of Laboratory Medicine, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 4. Department of Surgical, Medical & Molecular Pathology & Critical Care Medicine, University of Pisa, Pisa, Italy. 5. NEuroMuscular Omnicentre (NEMO), ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
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.
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 ALSpatients, 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.
Entities:
Keywords:
D-loop mitochondrial region; SOD1; amyotrophic lateral sclerosis; epigenetics; mitochondrial DNA methylation; mtDNA copy number
Authors: Rangariroyashe H Chipika; We Fong Siah; Mary Clare McKenna; Stacey Li Hi Shing; Orla Hardiman; Peter Bede Journal: J Neurol Date: 2020-10-31 Impact factor: 6.682
Authors: João A Amorim; Giuseppe Coppotelli; Anabela P Rolo; Carlos M Palmeira; Jaime M Ross; David A Sinclair Journal: Nat Rev Endocrinol Date: 2022-02-10 Impact factor: 47.564
Authors: Marta Gonzalez-Freire; A Zenobia Moore; Charlotte A Peterson; Kate Kosmac; Mary M McDermott; Robert L Sufit; Jack M Guralnik; Tamar Polonsky; Lu Tian; Melina R Kibbe; Michael H Criqui; Lingyu Li; Christian Leeuwenburgh; Luigi Ferrucci Journal: J Am Heart Assoc Date: 2020-03-21 Impact factor: 5.501