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Bouillaud 2012 Abstract Bioblast
Enzyme Complex I  + , Complex IV;cytochrome c oxidase  +
Has abstract [[File:Bouillaud-photo.JPG|right|200px|Fré
[[File:Bouillaud-photo.JPG|right|200px|Frédéric Bouillaud]]Sulfide (H<sub>2</sub>S gas, HS<sup>-</sup> anion) shows the same toxicity as cyanide, NO or CO for Complex IV (cytochrome oxidase; CIV). NO, CO and H<sub>2</sub>S are considered as gasotransmitters of physiological relevance. While signaling is expected to occur by different pathways, the question of involvement of mitochondria remains sometimes unresolved and particularly because some experiments used concentrations relevant to bioenergetics. Cellular metabolism generates low amount of sulfide and the activity of bacteria in the colonic lumen exposes the colonic wall to extracellular concentrations of sulfide [#60 µM], large enough to inhibit cellular respiration. Therefore, the question of sulfide disposal needs to be adressed. Mitochondria themselves appear as best candidate to explain sulfide disposal: a ''Sulfide Oxidation Unit'' (SOU) oxidizes sulfide into thiosulfate in many cell types in culture and in mitochondria from liver, heart or kidney. When sulfide is infused to mitochondria or cells at rates that stay within their sulfide oxidation capacities they oxidize it and maintain a low (<500 nM with cells) external concentration of sulfide well behind the toxic level (IC50 10-20 µM with cells). Notably, SOU activity could not be detected in brain mitochondria or neuroblastoma cells making them intolerant to sulfide. SOU is constituted by a sulfide quinone reductase (SQR) associated with a sulfur transferase and a dioxygenase. Present knowledge indicates that two molecules of H<sub>2</sub>S and one of oxygen (O<sub>2</sub>) are consumed by SOU to deliver two electrons to quinone. Then the stoichiometry for mitochondrial respiration based on sulfide oxidation is (1+0.5) O<sub>2</sub> / 2 H<sub>2</sub>S = 0.75 and for the same rate of electron transfer three times more oxygen are needed than with NADH/FADH<sub>2</sub> coenzymes. In consequence, infusing sulfide immediately and significantly increases oxygen consumption of respiring cells/mitochondria. Mitochondria show a high affinity for sulfide and its oxidation usually takes priority over ongoing mitochondrial oxidation processes. Something that is mandatory to ensure efficient sulfide disposal in presence of largely greater intracellular concentrations of other substrates. Extracellular sulfide is therefore a remarkable substrate: it could be used at nanomolar concentrations, its gaseous nature allows fast transfer to mitochondria without transporters, it is directly usable to reduce quinone without metabolic processing (including for example initial ATP consuming steps). This metabolic role of sulfide and its reductant properties contrast sharply with the other two gazotransmitters and particularly with NO which is pro-oxidant. There are still uncertainties about the lowest concentration of sulfide that SQR would ''detect'' but, in physiological conditions, the overlap between bioenergetically relevant and signaling concentrations appears even more likely with sulfide than with NO or CO. Colonocytes are adapted to high sulfide exposure. In these cells ''reverse bioenergetic reactions'' including reverse electron flux in Complex I are taking place to ensure continuation of a fast sulfide oxidation even if CIV is inhibited.
ulfide oxidation even if CIV is inhibited.  +
Has publicationkeywords Sulfide  + , Gasotransmitters  + , CHO cells  + , Colonocytes  +
Has title Bouillaud F (2012) Sulfide - a remarkable mitochondrial substrate. Mitochondr Physiol Network 17.12.  +
Instrument and method Oxygraph-2k  + , TIP2k  +
Mammal and model Human  +
MiP area Respiration  +
Pathways N  + , CIV  + , Other combinations  +
Respiration and regulation Coupling efficiency;uncoupling  + , Inhibitor  +
Tissue and cell CHO  +
Was published by MiPNetLab FR Paris Bouillaud F +
Was submitted in year 2012  +
Was submitted to event Bioblast 2012 +
Was written by Bouillaud F +
Categories Abstracts
Modification date
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08:26:20, 9 November 2016  +
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