Mitochondria and Epigenetics – Crosstalk in Homeostasis and Stress

Crosstalk between mitochondria and the nuclear epigenome represents bidirectional mitonuclear communication: mitochondria are essential mediators of epigenetic processes and, conversely, changes in epigenome regulate mitochondrial function. Mitochondrial DNA can be methylated, although its biological significance remains unknown. Mitochondria-mediated changes in the epigenome affect stress responses and longevity. Through epigenetic mechanisms cells integrate environmental stimuli to fine-tune gene expression levels. Mitochondrial function is essential to provide the intermediate metabolites necessary to generate and modify epigenetic marks in the nucleus, which in turn can regulate the expression of mitochondrial proteins. In this review we summarize the function of mitochondria in the regulation of epigenetic mechanisms as a new aspect of mitonuclear communication. We focus in particular on the most common epigenetic modifications – histone acetylation and histone and DNA methylation. We also discuss the emerging field of mitochondrial DNA (mtDNA) methylation, whose physiological role remains unknown. Finally, we describe the essential role of some histone modifications in regulating the mitochondrial unfolded protein response (UPRmt) and the mitochondrial stress-dependent lifespan extension. Through epigenetic mechanisms cells integrate environmental stimuli to fine-tune gene expression levels. Mitochondrial function is essential to provide the intermediate metabolites necessary to generate and modify epigenetic marks in the nucleus, which in turn can regulate the expression of mitochondrial proteins. In this review we summarize the function of mitochondria in the regulation of epigenetic mechanisms as a new aspect of mitonuclear communication. We focus in particular on the most common epigenetic modifications – histone acetylation and histone and DNA methylation. We also discuss the emerging field of mitochondrial DNA (mtDNA) methylation, whose physiological role remains unknown. Finally, we describe the essential role of some histone modifications in regulating the mitochondrial unfolded protein response (UPRmt) and the mitochondrial stress-dependent lifespan extension.