Mitoepigenetics and hepatocellular carcinoma

Abstract

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.

Interaction of Mitochondrial and Epigenetic Regulation in Hepatocellular Carcinoma

“…The exact correlation between nucleus and mitochondrion allows for the maintenance of mitochondrial structure and function. On the one hand, the nuclear gene expression is regulated by mitochondrial intermediates, like acetyl-CoA, ATP, NAD + , and s-adenosylmethionine, which are the link between the epigenome and calorie availability [47,66]. In addition to the production of epigenetic substrates, mitochondria may be modified in their DNA (mtDNA).…”

Mitoepigenetics and Its Emerging Roles in Cancer

“…Recently, in addition to mitogenetics, epigenetics in mitochondria (mitoepigenetics) also emerges as an important regulatory mode that is related to human physiology and disorders, such as stemness, drug addiction, neurodegenerative diseases, cardiovascular diseases and metabolic diseases (Wallace, 1992;Gómez-Durán et al, 2010;Manev and Dzitoyeva, 2013;Kalani et al, 2014;Sadakierska-Chudy et al, 2014;Ghosh et al, 2015;Gao D. et al, 2017;Stimpfel et al, 2018;Coppede and Stoccoro, 2019). Importantly, this kind of mode of action has also emerged to be associated with cancers (Ferreira et al, 2015;Lozano-Rosas et al, 2018). However, mitoepigenetics has not been well depicted.…”