The human colon hosts about 100 trillion microbes that acquire nutrients from undigested materials from our diet. In turn, cells lining the colon use the microbial metabolite butyrate as their primary energy source. The colon also houses bacteria that produce hydrogen sulfide, a respiratory poison, which is removed by the action of SQR (short for sulfide quinone oxidoreductase), an enzyme found in the mitochondrion. Both energy production from butyrate and hydrogen sulfide clearance require coenzyme Q10, a naturally occurring compound, posing the dilemma of how priority for competing processes is established. In work in press in Cell Chemical Biology, co-first authors Aaron Landry, Sojin Moon, and Hanseong Kim in the laboratories of Ruma Banerjee and Uhn-Soo Cho showed that SQR can form coenzyme A persulfide, which inhibits energy production from butyrate, and allows prioritization of hydrogen sulfide clearance to protect cells against poisoning. The team also reported crystal structures of human SQR, which revealed that hydrogen sulfide clearance relies on an unexpected chemical strategy involving a cysteine trisulfide.