Rhodoquinone-dependent electron transport chain is essential for Caenorhabditis elegans survival in hydrogen sulfide environments.

Hydrogen sulfide (HS) has traditionally been considered an environmental toxin for animal lineages; yet, it plays a signaling role in various processes at low concentrations. Mechanisms controlling HS in animals, especially in sulfide-rich environments, are not fully understood. The main detoxification pathway involves the conversion of HS into less harmful forms, through a mitochondrial oxidation pathway. The first step of this pathway oxidizes sulfide and reduces ubiquinone (UQ) through sulfide-quinone oxidoreductase (SQRD/SQOR). Because HS inhibits cytochrome oxidase and hence UQ regeneration, this pathway becomes compromised at high HS concentrations. The free-living nematode Caenorhabditis elegans feeds on bacteria and can face high sulfide concentrations in its natural environment. This organism has an alternative ETC that uses rhodoquinone (RQ) as the lipidic electron transporter and fumarate as the final electron acceptor. In this study, we demonstrate that RQ is essential for survival in sulfide. RQ-less animals (kynu-1 and coq-2e KO) cannot survive high HS concentrations, while UQ-less animals (clk-1 and coq-2a KO) exhibit recovery, even when provided with a UQ-deficient diet. Our findings highlight that sqrd-1 uses both benzoquinones and that RQ-dependent ETC confers a key advantage (RQ regeneration) over UQ in sulfide-rich conditions. C. elegans also faces cyanide, another cytochrome oxidase inhibitor, whose detoxification leads to HS production, via cysl-2. Our study reveals that RQ delays killing by the HCN-producing bacteria Pseudomonas aeruginosa PAO1. These results underscore the fundamental role that RQ-dependent ETC serves as a biochemical adaptation to HS environments, and to pathogenic bacteria producing cyanide and HS toxins.