Mitochondria signaling to the epigenome: A novel role for an old organelle

Epigenetic modifications influence gene expression programs ultimately dictating physiological outcomes. In the past decades, an increasing body of work has demonstrated that the enzymes that deposit and/or remove epigenetic marks on DNA or histones use metabolites as substrates or co-factors, rendering the epigenome sensitive to metabolic changes. In this context, acetyl-CoA and alpha-ketoglutarate have been recognized as critical for epigenetics, impinging on histone marks and nuclear DNA methylation patterns. Given that these metabolites are primarily generated in the mitochondria through the tricarboxylic acid cycle (TCA), the requirement of proper mitochondrial function for maintenance of the epigenetic landscape seems obvious. Nevertheless, it was not until recently when the epigenomic outcomes of mitochondrial dysfunction were tested, revealing mito-chondria's far-reaching impact on epigenetics. This review will focus on data that directly tested the role of mitochondria on the epigenetic landscape, the mechanisms by which mitochondrial dysfunction may dysregulate the epigenome and gene expression, and their potential implications to health and disease.

Automated summary

Epigenetic modifications are influenced by the metabolites generated in the mitochondria, particularly acetyl-CoA and alpha-ketoglutarate, which play critical roles in histone marks and nuclear DNA methylation patterns. Proper mitochondrial function is essential for maintaining the epigenetic landscape, and dysfunction in mitochondria can have a negative impact on epigenetics and gene expression.