A Case for Hydrogen Sulfide Metabolism as an Oxygen Sensing Mechanism

The ability to detect oxygen availability is a ubiquitous attribute of aerobic organisms. However, the mechanism(s) that transduce oxygen concentration or availability into appropriate physiological responses is less clear and often controversial. This review will make the case for oxygen-dependent metabolism of hydrogen sulfide (H₂S) and polysulfides, collectively referred to as reactive sulfur species (RSS) as a physiologically relevant O₂ sensing mechanism. This hypothesis is based on observations that H₂S and RSS metabolism is inversely correlated with O₂ tension, exogenous H₂S elicits physiological responses identical to those produced by hypoxia, factors that affect H₂S production or catabolism also affect tissue responses to hypoxia, and that RSS efficiently regulate downstream effectors of the hypoxic response in a manner consistent with a decrease in O₂. H₂S-mediated O₂ sensing is then compared to the more generally accepted reactive oxygen species (ROS) mediated O₂ sensing mechanism and a number of reasons are offered to resolve some of the confusion between the two.