Mitochondrial epigenetics: an unnoticed phenomenon in mitochondrial gene expression

Mitochondrial epigenetics

Abstract

Epigenetics provides important information regarding maintenance of the gene expression profile. Extensive studies have shown that nuclear DNA nucleotides as well as histone proteins surrounding this DNA undergo different modifications and thus help in regulating the nuclear gene expression. Mitochondrial DNA is equally important like nuclear DNA for survival of the cell. However, whether mtDNA also undergoes similar epigenetic changes for the regulation of gene expression, is largely unknown. In the recent past, a number of studies have shown some covalent modifications, such as methylation or hydroxymethylation in the mtDNA, which is proposed to play a pivotal epigenetic role in regulating the replication and transcription of mtDNA. Post-translational modifications of mitochondrial transcription factor A (TFAM) are also suggested to be important for epigenetic modulations in mtDNA. These observations introduce a novel concept of mitochondrial epigenetics that can be defined as the study of changes in the mtDNA that can modify heritable phenotype in mitochondria itself without changing the mtDNA sequence. But the detailed mechanism through which mtDNA undergoes epigenetic modifications, as well as its regulation, is not much clear. Mitochondrial dysfunction is a well-known cause for different types of diseases and recently it has also been shown that mtDNA is differentially methylated in various neurological and metabolic diseases. In most of these diseases, this differential methylation was found to be associated with altered mitochondrial gene expression, but the exact mechanism through which mtDNA methylation controls the gene expression, remains elusive. In this review, the mitochondrial epigenetic modifications and their relationship with the regulation of mitochondrial gene expression has been summarized. The mitochondrial epigenetic modifications in different diseases and its significance in pathogenesis has also been highlighted.