The crosstalk between mitochondria and the epigenetic landscape

Abstract

Mitochondria are well-recognized for their role in ATP and reactive oxygen species generation, in addition to producing intermediate metabolites through the TCA (tricarboxylic acid) cycle. The crosstalk between metabolism and epigenetic modifications in the nucleus is becoming increasingly evident but the extent to which mitochondrial metabolites are required for these effects remains largely unknown. We recently showed using a cell culture model of acute mitochondrial DNA (mtDNA) depletion that electron flow sustains a functional oxidative TCA cycle, which in turn is necessary to maintain histone acetylation in the nucleus. Following this work, we have interrogated genome-wide locus specific changes in histone acetylation and in DNA methylation, and the extent to which these regulate gene expression. The time-wise progression and the signals associated with these events will be discussed.