H 2 S metabolism in colon cancer cells: Effect of hypoxia

Hydrogen sulfide (H2S) plays key roles in human (patho)physiology. Synthesized endogenously by known enzymatic systems, H2S is mainly metabolized through a mitochondrial sulfide-oxidizing pathway that comprises sulfide:quinone oxidoreductase (SQR) and a few other enzymes. H2S degradation through this pathway is coupled to electron injection into the respiratory chain and, thus, to stimulation of ATP synthesis. In cancer cells, H2S was reported to be synthesized at high levels and to stimulate energy metabolism and cell proliferation. Under hypoxic conditions, commonly found in the microenvironment of solid tumours, H2S is known to be more stable and to be overproduced with pro-survival effects. Here, H2S catabolism was investigated in colon cancer model cells grown under either normoxic (20% O2) or hypoxic (1% O2) conditions, comparing their maximal ability to dispose H2S at the level of the mitochondrion by high resolution respirometry. Intriguingly, cell exposure to hypoxic conditions was found to have effects on H2S metabolism, both in functional terms and at the level of protein expression. The potential implications of these findings will be discussed.