Do our cells use cyanide to communicate?

A team from the University of Fribourg has gathered compelling evidence that cyanide, a powerful poison even in small doses, is used in minute doses by the cells of our body to communicate.

The mere mention of the word cyanide arouses fear and conjures up images of spy films. But, as early as the 15th century, Paracelsus remarked "everything is poison, nothing is poison, it is the dose that makes the poison". Professor Csaba Szabo and his team have discovered that our cells produce cyanide gas in minute amounts and use it to activate certain processes. Cyanide thus joins the list of the three other gases known as gaseous transmitters: nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S). Thanks to the small size of their molecules, these gases can easily penetrate the membranes that separate cells and are therefore a practical means of passing signals between cells.

It’s all in the dosage
«In the 1990s,» explains Professor Szabo, «it was discovered that nitric oxide was a very important mediating gas in cells. This was a great surprise, because it is toxic in relatively low doses. Ten years later it was the same story with CO and in recent years with H2S, hydrogen sulphide.» In each case, a toxic gas is used in extremely small doses to regulate a large number of processes in our cells.

With a converging body of evidence, Professor Szabo's team now suggests the addition of cyanide as the fourth gaseous transmitter, as indicated by the results published in mai in the journal PNAS. They particularly used bacteria which produce cyanide naturally, and observed, under laboratory conditions, the stimulating effect on living human cells such as liver cells.

Cyanide as a regulator
The production of cyanide in the body at very low doses was already known. What the team has shown, and which strongly suggests a biological role, is that cyanide has a positive and stimulating effect on certain cellular mechanisms at very small doses, and then a deleterious and blocking effect at larger doses. This behaviour – positive effect, then negative as the dose increases – Is typical of gaseous transmitters. Its effect is particularly evident on the mitochondria, those essential organelles that provide our cells with energy.

This result opens up a whole new field of research into the cellular mechanisms of life. The most important thing," says Professor Szabo, "is what happens now. We need to clarify how and why cyanide is produced and used as a transmitter. In particular, it may be that it is involved in certain diseases.”

In fact, Professor Szabo recently highlighted the link between certain symptoms of Down's syndrome and the production of hydrogen sulphide (H2S) as a transmitter, a striking example of a link between a gaseous transmitter and a serious disease.

> The PNAS article: «Physiological concentrations of cyanide stimulate mitochondrial Complex IV and enhance cellular bioenergetics», Elisa B. Randi, Karim Zuhra, Laszlo Pecze, Theodora Panagaki and Csaba Szabo, 2021, PNAS, May 10.