Mitoepigenetics: An intriguing regulatory layer in aging and metabolic-related diseases

Abstract

As a key organelle in eukaryotic cells, mitochondria play a central role in maintaining normal cellular functions. Mitochondrial dysfunction is reported to be closely related with aging and various diseases. Epigenetic modifications in nuclear genome provide a substantial layer for the modulation of nuclear-encoded gene expression. However, whether mitochondria could also be subjected to such similar epigenetic alterations and the involved mechanisms remain largely obscure and controversial. Recently, accumulating evidence has suggested that mitochondrial epigenetics, also known as mitoepigenetics may serve as an intriguing regulatory layer in mitochondrial DNA (mtDNA)-encoded gene expression. Given the potential regulatory role of mitoepigenetics, mitochondrial dysfunction derived from mitoepigenetics-induced abnormal gene expression could also be closely associated with aging and disease development. In this review, we summarized the recent advances in mitoepigenetics, with a special focus on mtDNA methylation in aging and metabolic-related diseases as well as the new methods and technologies for the study of mitoepigenetics. Uncovering the regulatory role of mitoepigenetics will help to understand the underlying mechanisms of mitochondrial dysfunction and provide novel strategies for delaying aging and preventing metabolic-related diseases.

Keywords: Mitochondrial DNA (mtDNA) methylation; Mitochondrial epigenetics (mitoepigenetics); Mitochondrial non-coding RNAs (ncRNAs); Post-translational modifications (PTMs); mtDNA-associated proteins.