Signaling Integration of Hydrogen Sulfide and Iron on Cellular Functions

Hydrogen sulfide (H₂S) is an endogenous signaling molecule, regulating numerous physiological functions from vasorelaxation to neuromodulation. Iron is a well-known bioactive metal ion, being the central component of hemoglobin for oxygen transportation and participating in biomolecule degradation, redox balance, and enzymatic actions. The interplay between H₂S and iron metabolisms and functions impacts significantly on the fate and wellness of different types of cells. Iron level in vivo affects the production of H₂S via nonenzymatic reactions. On the contrary, H₂S quenches excessive iron inside the cells and regulates the redox status of iron. Abnormal metabolisms of both iron and H₂S are associated with various conditions and diseases such as iron overload, anemia, oxidative stress, and cardiovascular and neurodegenerative diseases. The molecular mechanisms for the interactions between H₂S and iron are unsettled yet. Here we review signaling links of the production, metabolism, and their respective and integrative functions of H₂S and iron in normalcy and diseases. Physiological and pathophysiological importance of H₂S and iron as well as their therapeutic applications should be evaluated jointly, not separately. Future investigation should expand from iron-rich cells and tissues to the others, in which H₂S and iron interaction has not received due attention. Antioxid. Redox Signal. 36, 275-293.