The biological regulatory system through which the organism responds to environmental pressures is mediated by epigenetic modifications of the genome without altering the DNA sequence. Among the epigenetic processes, DNA methylation is perhaps the best understood epigenetic adaption and most common DNA modification. This mechanism plays an important role in regulating the gene expression of many biological processes and has wide-ranging effects on health. Aberrant epigenetic regulation has been described in many human diseases. Concretely, there is growing body of evidence that shows a relevant role of epigenetic marks with obesity and its co-disease susceptibility. However, while nuclear DNA methylation is a well stablished feature, very little attention has been devoted to mitochondrial epigenetics. Obesity is often associated with a state of mild chronic inflammation characterized by an abnormal production of proinflammatory and prooxidant mediators. This proinflammatory condition has been linked to a mitochondrial dysfuncion. In fact, an energy restriction therapy devised to lose weight induces an increase in the intracellular ATP content and mitochondrial-related gene expression, concomitantly with a decrease oxidative stress and inflammatory markers. Mitochondrial dysfunction and the increment of mitochondrial Reactive Oxygen Species (ROS) production are important benchmarks of the aging and metabolic disturbances development. Therefore, the mitochondrial dysfunction might be critically involved in the pathogenesis of obesity. However, the molecular mechanisms leading to mitochondrial dysfunction in metabolic diseases are still unknown. In this context, mitochondrial epigenetics is a novel mechanism to understand the pathobiology of diseases with a mitochondrial dysfunction involvement. Epigenetic regulation of mtDNA has received increasing attention in the last years due to its implication in clinically relevant disease. Variations in mtDNA methylation were associated with exposure to pollutants and Nonalcoholic fatty liver disease (NAFLD) and were proposed to have a role in mitochondrial gene expression regulation. mtDNA methylation was reported to be induced by hyperglycaemia in retinal endothelial cells and to negatively regulate mitochondrial gene expression. Moreover, mitochondrial epigenetic can modulate nuclear DNA and nuclear DNA epigenetic may affect mtDNA. Hence, abnormal mtDNA methylation is attracting increasing attention as potential biomarker and might have therapeutic potential for metabolic diseases management.
20 - 23 May 2017
European Society of Endocrinology