Memory of ancestral mitochondrial stress

https://www.nature.com/articles/s41556-018-0255-4

Sarah-Lena Offenburg, Marcos Francisco Perez and Ben Lehner

A WORD ON EPIGENETIC MODIFICATIONS
There are two main types of epigenetic modifications, DNA methylation and histone modifications.

In DNA methylations, a methyl group is added to DNA. These reactions are catalysed by enzymes known as DNA methyltransferases. This modification result in the creation binding sites for other proteins, which bind and recruit or are associated with other proteins which can act on histones (determining histone modifications, see below).In eukaryotes, the most prevalent DNA methylation concerns cytosine nucleotides and gives origin to 5-methylcytosine.

Histone modifications affect the DNA-protein interactions, modifying the structure of chromatin (mixture of DNA and proteins which form chromosomes). This, in turn, alters the ability for a gene to be transcribed and expressed. 

THE RECENT FINDING

Dna methylation was thought to be absent in the roundworm C. elegans, since its genome does not contain 5-methylcytosine. Another methylation, N6-methyldeoxyadenine (6mA) was recently detected in C. elegans (and other species), but its functions remain elusive.

In a recent work, published in Nature Cell Biology, Ma et al. show that C. elegans can inherit resistance to stress and give evidence for the involvement of 6mA into this process.

The authors used antimycin, an antibiotic, to stress the mitochondria of the roundworm. The effect of antimycin is to inhibit the mitochondrial respiratory chain and that, in turn, slows down the development of worms. 

It was observed the progeny of animals exposed to the antibiotic developed faster when exposed to the same stressor. Unexposed offspring was protected up to four generations.

Interestingly, the resistance is not inherited through mitochondria themselves, since it can also be transmitted through male parents.

The authors found that the worms defective in a specific histone modification (H3K4me3) were unable to inherit resistance. A previous study in C. elegans showed a crosstalk between H3K4me3 and the methylation 6mA. Moreover, animals deficient in a known 6mA me methyltransferase were unable to transmit the resistance.

Open questions remain about the precise roles of 6mA and H3K4me3 in the observed phenomenon.

The involvement of mitochondria is important because C. elegans may be exposed to bacteria-induced mitochondrial stress in its natural habitat, which makes the finding more relevant. The inheritance of this stress resistance is one of the few documented cases of a trans-generational memory of a kind of stimulus which can occur in nature.