title: Altered Mitochondrial DNA Methylation Pattern in Alzheimer Disease-Related Pathology and in Parkinson Disease.
abstract: Mitochondrial dysfunction is linked with the etiopathogenesis of Alzheimer disease and Parkinson disease. Mitochondria are intracellular organelles essential for cell viability and are characterized by the presence of the mitochondrial (mt)DNA. DNA methylation is a well-known epigenetic mechanism that regulates nuclear gene transcription. However, mtDNA methylation is not the subject of the same research attention. The present study shows the presence of mitochondrial 5-methylcytosine in CpG and non-CpG sites in the entorhinal cortex and substantia nigra of control human postmortem brains, using the 454 GS FLX Titanium pyrosequencer. Moreover, increased mitochondrial 5-methylcytosine levels are found in the D-loop region of mtDNA in the entorhinal cortex in brain samples with Alzheimer disease-related pathology (stages I to II and stages III to IV of Braak and Braak; n = 8) with respect to control cases. Interestingly, this region shows a dynamic pattern in the content of mitochondrial 5-methylcytosine in amyloid precursor protein/presenilin 1 mice along with Alzheimer disease pathology progression (3, 6, and 12 months of age). Finally, a loss of mitochondrial 5-methylcytosine levels in the D-loop region is found in the substantia nigra in Parkinson disease (n = 10) with respect to control cases. In summary, the present findings suggest mtDNA epigenetic modulation in human brain is vulnerable to neurodegenerative disease states.
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Blanch
authors.affiliation: Department of Statistics, University of Barcelona, Barcelona, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Mosquera
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Ansoleaga
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain; Networked Biomedical Research Centre for NeuroDegenerative Disorders (CIBERNED), Madrid, Spain; Departament of Pathology and Experimental Therapeutics, University of Barcelona, L'Hospitalet de Llobregat, Spain.
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain; Networked Biomedical Research Centre for NeuroDegenerative Disorders (CIBERNED), Madrid, Spain. Electronic address: mbarrachina@idibell.cat.
authors.forename: Marta
authors.initials: M
authors.lastname: Barrachina
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D019175:DNA Methylation / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D004272:DNA, Mitochondrial