Signaling Integration of Hydrogen Sulfide and Iron on Cellular Functions

Significance: 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. Recent Advances: 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. Critical Issues: 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. Future Directions: 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.