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Mitochondria, the power plants of the cell, are the descendants of ancient symbiotic bacteria, and still carry a remnant circular genome, separately from the DNA of the cell nucleus. Some forms of mutational damage to mitochondrial DNA, and the downstream consequences of that damage, are thought to be an important contributing cause of degenerative aging, but what about epigenetic changes? Epigenetic aging in nuclear DNA is a hot topic at the moment, so it is inevitable that attention would turn to the epigenetics of the much smaller mitochondrial genome.
Inflammation is a defining factor in disease progression; epigenetic modifications of this first line of defence pathway can affect many physiological and pathological conditions, like aging and tumorigenesis. Inflammageing, one of the hallmarks of aging, represents a chronic, low key but a persistent inflammatory state. Oxidative stress, alterations in mitochondrial DNA (mtDNA) copy number and mis-localized extra-mitochondrial mtDNA are suggested to directly induce various immune response pathways. This could ultimately perturb cellular homeostasis and lead to pathological consequences.
Epigenetic remodelling of mtDNA by DNA methylation, post-translational modifications of mtDNA binding proteins and regulation of mitochondrial gene expression by nuclear DNA or mtDNA encoded non-coding RNAs, are suggested to directly correlate with the onset and progression of various types of cancer. Mitochondria are also capable of regulating immune response to various infections and tissue damage by producing pro- or anti-inflammatory signals. This occurs by altering the levels of mitochondrial metabolites and reactive oxygen species (ROS) levels.
Since mitochondria are known as the guardians of the inflammatory response, it is plausible that mitochondrial epigenetics might play a pivotal role in inflammation. Thus, strategies aimed at compensating for changes brought about by mitochondrial epigenetics like restoration of dysfunctional mtDNA or TFAM activity might emerge as promising preventive and therapeutic interventions for pathological conditions occurring due to exacerbated inflammation.