Mitoepigenetics and hepatocellular carcinoma

Mitochondria are the center of energy production in eukaryotic cells and are crucial for several cellular processes. Dysfunctional mitochondria have been associated with cancer progression. Mitochondria contain their own circular DNA (mtDNA), which codes for 13 proteins, 2rRNA, 22tRNA and non-coding RNAs. Recent evidence showed the presence of 5-methylcytosine and 5-hydroximethylcytosine in mtDNA suggesting that the level of gene expression could be modulated like a nuclear DNA by direct epigenetic modifications. Mitoepigenetics is a bidirectional phenomenon in the epigenetic regulation of mitochondrial genes encoded in both the nucleus and the mitochondrion. This process is affected by SAM-mediated methylation and hydroxymethylation of mtDNA and by nuclear chromatin modulators from mitochondria, such as Acetyl-CoA and NAD. There is some information about physiological and pathological methylated profiles, but information is scarce for hepatocellular carcinoma (HCC). The aim of this review is to summarize the mitoepigenetic knowledge in HCC already reported so far, through a keywords search in Medline. In addition, the deregulation of energy intermediaries needed for the mitoepigenetic regulation is described. As this is a new area of study, a rigorous analysis and careful interpretation and integration of results are needed.