IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Mitochondrial dysfunction and aberrant methylation in nuclear genes
Autor/es:
MAYORGA, LIA; LAURITO, SERGIO; EIROA, HERNAN; LOOS, MARIANA; CAMPOY, EMANUEL MARTIN; ROQUÉ, MARÍA
Lugar:
Barcelona
Reunión:
Congreso; European Society of Human Genetics (ESHG); 2016
Resumen:
Introduction: It is known that the environment has an impact on epigenomes, especially of cancer cells. It is, however, still not clear how this occurs. A key hallmark of cancer cells is energy reprogramming whereby glycolysis is preferred over OXPHOS. We propose that changes in mitochondria might play a role in epigenome modifications. The aim of this study was therefore to investigate the role of mitochondrial dysfunction in aberrant methylation of nuclear genes.Methods: Methylation analyses of 26 cancer related nuclear genes were performed by MS-MLPA assay on: -leucocytes and muscle samples from 23 mitochondrial disease patients; -human skeletal muscle (HSkM) cell line treated with Rotenone, an OXPHOS inhibitor. OXPHOS function was determined by Trimethylrodamine esther stain and quantifications on confocal microscopy were performed using ImageJ. Methylation was analyzed by GeneMarker v1.95. Results: muscle samples from patients presented higher frequency of aberrantly methylated genes than leucocytes (p=0,02). Caspase8 was the most frequently methylated gene in muscle (76,9% vs 0% in leucocytes). Unexpectedly, experiments in OXPHOS inhibited HSkM cells revealed changes in the methylation of a single gene: Caspase8. The methylation status of this gene was augmented when the mitochondrial membrane potential came down due to Rotenone action and reverted when Rotenone was removed. Conclusions: Our observations indicate that mitochondria?s dysfunction is related to methylation alterations in nuclear genes. These epigenetic findings could contribute in the practice, to explain the wide phenotypic spectrum of mitochondrial diseases. In addition, this suggests that mitochondrias have a potential role in the link between environment and epigenome.