Worm Biology Lab, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Worm Biology Lab, Institut Pasteur de Montevideo, Montevideo, Uruguay; Laboratorio de Química Farmacéutica, Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
J Biol Chem. 2024 Sep;300(9):107708. doi: 10.1016/j.jbc.2024.107708. Epub 2024 Aug 22.
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.
硫化氢 (HS) 传统上被认为是动物谱系中的环境毒素；然而，在低浓度下，它在各种过程中发挥着信号作用。动物中控制 HS 的机制，特别是在富含硫化物的环境中，尚未完全理解。主要的解毒途径是通过线粒体氧化途径将 HS 转化为危害较小的形式。该途径的第一步通过硫化物-醌氧化还原酶 (SQRD/SQOR) 将硫化物氧化并还原泛醌 (UQ)。由于 HS 抑制细胞色素氧化酶，从而抑制 UQ 的再生，因此在高 HS 浓度下，该途径会受到损害。自由生活的线虫秀丽隐杆线虫以细菌为食，在其自然环境中可能会面临高浓度的硫化物。该生物体具有替代的电子传递链，使用 rhodoquinone (RQ) 作为脂溶性电子载体，延胡索酸盐作为最终电子受体。在这项研究中，我们证明了 RQ 对于在硫化物中生存是必不可少的。缺乏 RQ 的动物（kynu-1 和 coq-2e KO）无法在高 HS 浓度下存活，而缺乏 UQ 的动物（clk-1 和 coq-2a KO）即使在提供缺乏 UQ 的饮食时也能恢复。我们的发现强调了 sqrd-1 同时使用苯醌，并且依赖 RQ 的电子传递链在富含硫化物的条件下比 UQ 具有关键优势（RQ 再生）。秀丽隐杆线虫还面临另一种细胞色素氧化酶抑制剂氰化物，其解毒作用通过 cysl-2 导致 HS 的产生。我们的研究表明，RQ 可延迟产氰 Pseudomonas aeruginosa PAO1 细菌的杀伤作用。这些结果强调了依赖 RQ 的电子传递链作为对 HS 环境和产生氰化物和 HS 毒素的致病性细菌的生化适应的基本作用。
