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Property "Has-20abstract" (as page type) with input value "-5B-5BFile:Bouillaud-2Dphoto.JPG-7Cright-7C200px-7CFrédéric-20Bouillaud-5D-5DSulfide-20(H-3Csub-3E2-3C-2Fsub-3ES-20gas,-20HS-3Csup-3E-2D-3C-2Fsup-3E-20anion)-20shows-20the-20same-20toxicity-20as-20cyanide,-20NO-20or-20CO-20for-20Complex-20IV-20(cytochrome-20oxidase-3B-20CIV).-20NO,-20CO-20and-20H-3Csub-3E2-3C-2Fsub-3ES-20are-20considered-20as-20gasotransmitters-20of-20physiological-20relevance.-20While-20signaling-20is-20expected-20to-20occur-20by-20different-20pathways,-20the-20question-20of-20involvement-20of-20mitochondria-20remains-20sometimes-20unresolved-20and-20particularly-20because-20some-20experiments-20used-20concentrations-20relevant-20to-20bioenergetics.-20Cellular-20metabolism-20generates-20low-20amount-20of-20sulfide-20and-20the-20activity-20of-20bacteria-20in-20the-20colonic-20lumen-20exposes-20the-20colonic-20wall-20to-20extracellular-20concentrations-20of-20sulfide-20-5B-2360-20µM-5D,-20large-20enough-20to-20inhibit-20cellular-20respiration.-20Therefore,-20the-20question-20of-20sulfide-20disposal-20needs-20to-20be-20adressed.-20Mitochondria-20themselves-20appear-20as-20best-20candidate-20to-20explain-20sulfide-20disposal:-20a-20-27-27Sulfide-20Oxidation-20Unit-27-27-20(SOU)-20oxidizes-20sulfide-20into-20thiosulfate-20in-20many-20cell-20types-20in-20culture-20and-20in-20mitochondria-20from-20liver,-20heart-20or-20kidney.-20When-20sulfide-20is-20infused-20to-20mitochondria-20or-20cells-20at-20rates-20that-20stay-20within-20their-20sulfide-20oxidation-20capacities-20they-20oxidize-20it-20and-20maintain-20a-20low-20(-3C500-20nM-20with-20cells)-20external-20concentration-20of-20sulfide-20well-20behind-20the-20toxic-20level-20(IC50-2010-2D20-20µM-20with-20cells).-20Notably,-20SOU-20activity-20could-20not-20be-20detected-20in-20brain-20mitochondria-20or-20neuroblastoma-20cells-20making-20them-20intolerant-20to-20sulfide.-20SOU-20is-20constituted-20by-20a-20sulfide-20quinone-20reductase-20(SQR)-20associated-20with-20a-20sulfur-20transferase-20and-20a-20dioxygenase.-20Present-20knowledge-20indicates-20that-20two-20molecules-20of-20H-3Csub-3E2-3C-2Fsub-3ES-20and-20one-20of-20oxygen-20(O-3Csub-3E2-3C-2Fsub-3E)-20are-20consumed-20by-20SOU-20to-20deliver-20two-20electrons-20to-20quinone.-20Then-20the-20stoichiometry-20for-20mitochondrial-20respiration-20based-20on-20sulfide-20oxidation-20is-20(1+0.5)-20O-3Csub-3E2-3C-2Fsub-3E-20-2F-202-20H-3Csub-3E2-3C-2Fsub-3ES-20=-200.75-20and-20for-20the-20same-20rate-20of-20electron-20transfer-20three-20times-20more-20oxygen-20are-20needed-20than-20with-20NADH-2FFADH-3Csub-3E2-3C-2Fsub-3E-20coenzymes.-20In-20consequence,-20infusing-20sulfide-20immediately-20and-20significantly-20increases-20oxygen-20consumption-20of-20respiring-20cells-2Fmitochondria.-0A-0AMitochondria-20show-20a-20high-20affinity-20for-20sulfide-20and-20its-20oxidation-20usually-20takes-20priority-20over-20ongoing-20mitochondrial-20oxidation-20processes.-20Something-20that-20is-20mandatory-20to-20ensure-20efficient-20sulfide-20disposal-20in-20presence-20of-20largely-20greater-20intracellular-20concentrations-20of-20other-20substrates.-20Extracellular-20sulfide-20is-20therefore-20a-20remarkable-20substrate:-20it-20could-20be-20used-20at-20nanomolar-20concentrations,-20its-20gaseous-20nature-20allows-20fast-20transfer-20to-20mitochondria-20without-20transporters,-20it-20is-20directly-20usable-20to-20reduce-20quinone-20without-20metabolic-20processing-20(including-20for-20example-20initial-20ATP-20consuming-20steps).-20This-20metabolic-20role-20of-20sulfide-20and-20its-20reductant-20properties-20contrast-20sharply-20with-20the-20other-20two-20gazotransmitters-20and-20particularly-20with-20NO-20which-20is-20pro-2Doxidant.-20There-20are-20still-20uncertainties-20about-20the-20lowest-20concentration-20of-20sulfide-20that-20SQR-20would-20-27-27detect-27-27-20but,-20in-20physiological-20conditions,-20the-20overlap-20between-20bioenergetically-20relevant-20and-20signaling-20concentrations-20appears-20even-20more-20likely-20with-20sulfide-20than-20with-20NO-20or-20CO.-0A-0AColonocytes-20are-20adapted-20to-20high-20sulfide-20exposure.-20In-20these-20cells-20-27-27reverse-20bioenergetic-20reactions-27-27-20including-20reverse-20electron-20flux-20in-20Complex-20I-20are-20taking-20place-20to-20ensure-20continuation-20of-20a-20fast-20sulfide-20oxidation-20even-20if-20CIV-20is-20inhibited." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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