DNA methyltransferase DAMT-1 catalyzes in C. elegans a specific form of epigenetic mark, adenosine N6-methylation (6mA), on mitochondrial DNA (mtDNA). Impaired regulation of this modification facilitates propagation of mutant mtDNA, impairs mitochondrial function, and contributes to organismal aging. This is reported by a study published in Cell Metabolism.

Mitochondria are responsible for generating chemical energy in the cell and possess their own DNA. The mitochondrial genome is present in multiple copies in the mitochondria and includes genes that, among others, encode proteins forming part of respiration chain complexes. How exactly mitochondrial gene expression and the number of mtDNA copies are controlled has not yet been fully elucidated.

The authors of the study investigated the role of mtDNA 6mA in the model organism of the nematode worm C. elegans. They showed that DAMT-1 and ALKB-1, a demethylase, are localized in mitochondria and crucial for the presence of 6mA methylation on mtDNA. In their experiments, targeted modulation of the two enzymes’ activities resulted in changes in the number of mtDNA copies and transcript levels, reduced oxidative phosphorylation, increased oxidative stress and a shortened lifespan.