Publications

• A fission yeast gene for mitochondrial sulfide oxidation.

  Vande Weghe J.G., Ow D.W.

  A cadmium-hypersensitive mutant of the fission yeast Schizosaccharomyces pombe was found to accumulate abnormally high levels of sulfide. The gene required for normal regulation of sulfide levels, hmt2(+), was cloned by complementation of the cadmium-hypersensitive phenotype of the mutant. Cell fr ... >> More

  A cadmium-hypersensitive mutant of the fission yeast Schizosaccharomyces pombe was found to accumulate abnormally high levels of sulfide. The gene required for normal regulation of sulfide levels, hmt2(+), was cloned by complementation of the cadmium-hypersensitive phenotype of the mutant. Cell fractionation and immunocytochemistry indicated that HMT2 protein is localized to mitochondria. Sequence analysis revealed homology between HMT2 and sulfide dehydrogenases from photosynthetic bacteria. HMT2 protein, produced in and purified from Escherichia coli, was soluble, bound FAD, and catalyzed the reduction of quinone (coenzyme Q2) by sulfide. HMT2 activity was also detected in isolated fission yeast mitochondria. We propose that HMT2 functions as a sulfide:quinone oxidoreductase. Homologous enzymes may be widespread in higher organisms, as sulfide-oxidizing activities have been described previously in animal mitochondria, and genes of unknown function, but with similarity to hmt2(+), are present in the genomes of flies, worms, rats, mice, and humans. << Less

  J. Biol. Chem. 274:13250-13257(1999) [PubMed] [EuropePMC]

• Organization of the human mitochondrial hydrogen sulfide oxidation pathway.

  Libiad M., Yadav P.K., Vitvitsky V., Martinov M., Banerjee R.

  Sulfide oxidation is expected to play an important role in cellular switching between low steady-state intracellular hydrogen sulfide levels and the higher concentrations where the physiological effects are elicited. Yet despite its significance, fundamental questions regarding how the sulfide oxi ... >> More

  Sulfide oxidation is expected to play an important role in cellular switching between low steady-state intracellular hydrogen sulfide levels and the higher concentrations where the physiological effects are elicited. Yet despite its significance, fundamental questions regarding how the sulfide oxidation pathway is wired remain unanswered, and competing proposals exist that diverge at the very first step catalyzed by sulfide quinone oxidoreductase (SQR). We demonstrate that, in addition to sulfite, glutathione functions as a persulfide acceptor for human SQR and that rhodanese preferentially synthesizes rather than utilizes thiosulfate. The kinetic behavior of these enzymes provides compelling evidence for the flow of sulfide via SQR to glutathione persulfide, which is then partitioned to thiosulfate or sulfite. Kinetic simulations at physiologically relevant metabolite concentrations provide additional support for the organizational logic of the sulfide oxidation pathway in which glutathione persulfide is the first intermediate formed. << Less

  J. Biol. Chem. 289:30901-30910(2014) [PubMed] [EuropePMC]

• Human sulfide:quinone oxidoreductase catalyzes the first step in hydrogen sulfide metabolism and produces a sulfane sulfur metabolite.

  Jackson M.R., Melideo S.L., Jorns M.S.

  Sulfide:quinone oxidoreductase (SQOR) is a membrane-bound enzyme that catalyzes the first step in the mitochondrial metabolism of H(2)S. Human SQOR is successfully expressed at low temperature in Escherichia coli by using an optimized synthetic gene and cold-adapted chaperonins. Recombinant SQOR c ... >> More

  Sulfide:quinone oxidoreductase (SQOR) is a membrane-bound enzyme that catalyzes the first step in the mitochondrial metabolism of H(2)S. Human SQOR is successfully expressed at low temperature in Escherichia coli by using an optimized synthetic gene and cold-adapted chaperonins. Recombinant SQOR contains noncovalently bound FAD and catalyzes the two-electron oxidation of H(2)S to S(0) (sulfane sulfur) using CoQ(1) as an electron acceptor. The prosthetic group is reduced upon anaerobic addition of H(2)S in a reaction that proceeds via a long-wavelength-absorbing intermediate (λ(max) = 673 nm). Cyanide, sulfite, or sulfide can act as the sulfane sulfur acceptor in reactions that (i) exhibit pH optima at 8.5, 7.5, or 7.0, respectively, and (ii) produce thiocyanate, thiosulfate, or a putative sulfur analogue of hydrogen peroxide (H(2)S(2)), respectively. Importantly, thiosulfate is a known intermediate in the oxidation of H(2)S by intact animals and the major product formed in glutathione-depleted cells or mitochondria. Oxidation of H(2)S by SQOR with sulfite as the sulfane sulfur acceptor is rapid and highly efficient at physiological pH (k(cat)/K(m,H(2)S) = 2.9 × 10(7) M(-1) s(-1)). A similar efficiency is observed with cyanide, a clearly artificial acceptor, at pH 8.5, whereas a 100-fold lower value is seen with sulfide as the acceptor at pH 7.0. The latter reaction is unlikely to occur in healthy individuals but may become significant under certain pathological conditions. We propose that sulfite is the physiological acceptor of the sulfane sulfur and that the SQOR reaction is the predominant source of the thiosulfate produced during H(2)S oxidation by mammalian tissues. << Less

  Biochemistry 51:6804-6815(2012) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria.

  Hildebrandt T.M., Grieshaber M.K.

  Hydrogen sulfide is a potent toxin of aerobic respiration, but also has physiological functions as a signalling molecule and as a substrate for ATP production. A mitochondrial pathway catalyzing sulfide oxidation to thiosulfate in three consecutive reactions has been identified in rat liver as wel ... >> More

  Hydrogen sulfide is a potent toxin of aerobic respiration, but also has physiological functions as a signalling molecule and as a substrate for ATP production. A mitochondrial pathway catalyzing sulfide oxidation to thiosulfate in three consecutive reactions has been identified in rat liver as well as in the body-wall tissue of the lugworm, Arenicola marina. A membrane-bound sulfide : quinone oxidoreductase converts sulfide to persulfides and transfers the electrons to the ubiquinone pool. Subsequently, a putative sulfur dioxygenase in the mitochondrial matrix oxidizes one persulfide molecule to sulfite, consuming molecular oxygen. The final reaction is catalyzed by a sulfur transferase, which adds a second persulfide from the sulfide : quinone oxidoreductase to sulfite, resulting in the final product thiosulfate. This role in sulfide oxidation is an additional physiological function of the mitochondrial sulfur transferase, rhodanese. << Less

  FEBS J 275:3352-3361(2008) [PubMed] [EuropePMC]