Hydrogen sulfide and cell signaling: Team player or referee?

Hydrogen sulfide (H2S) has been postulated to be the third gasotransmitter, and along with other reactive compounds such as reactive oxygen species (ROS) and nitric oxide (NO) it is thought to be a key signalling molecule. Enzymes which generate H2S, and remove it, have been characterised in both plants and animals and although it is inherently toxic to cells - inhibiting cytochrome oxidase for example H2S is now being thought of as part of signal transduction pathways. But is it working as a signal in the sense usually seen for small signalling molecules, that is, produced when needed, perceived and leading to dedicated responses in cells? A look through the literature shows that H2S is involved in many stress responses, and in animals is implicated in the onset of many diseases, in both cases where ROS and NO are often involved. It is suggested here that H2S is not acting as a true signal, but through its interaction with NO and ROS metabolism is modulating such activity, keeping it in check unless strictly needed, and that H2S is acting as a referee to ensure NO and ROS metabolism is working properly. (C) 2014 Elsevier Masson SAS. All rights reserved.