H2S metabolism in colon cancer cells exposed to hypoxia

Hydrogen sulfide (H2S), after nitric oxide (NO) and carbon monoxide (CO), is known as the third gasotransmitter. Involved in antioxidant protection and regulation of different physiological functions, H2S is synthesized by cystathionine β-synthase (CBS) and few other enzymes, and is oxidatively catabolized in the mitochondrion, where H2S-derived electrons are transferred to coenzyme Q by sulfide quinone oxidoreductase (SQR), stimulating respiration and ATP production. Metabolic and oncologic diseases are related to dysregulation of H2S metabolism. Hence the importance of understanding how H2S bioavailability is regulated under (patho)physiological conditions. We previously reported that both CO and NO negatively modulate CBS with high affinity especially in the presence of its allosteric activator S-adenosyl-L-methionine, and that a CBS variant responsible for classical homocystinuria shows an unusual high propensity to CO inhibition, suggesting a novel pathogenic mechanism. Here, by investigating the effect of hypoxia on H2S catabolism in colon cancer, we report that hypoxia-treated SW480 cells have overall reduced ability to detoxify H2S and less mitochondria but enriched in SQR. These data suggest that under hypoxic conditions, while the lower sulphide-detoxifying activity contributes to ensure higher protective H2S levels against O2 deprivation, mitochondria get enriched in SQR to afford protection from H2S poisoning