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    Mitochondrial oxidation of hydrogen sulfide (H2S)



     Frédéric Bouillaud - Phone +33 1 53 73 27 50





    Hydrogen sulfide (H2S) is a gas released by volcanoes or by anaerobic ecosystems including the gut microbiota. Normal cellular metabolism also generates H2S.

    H2S, NO, CO and cyanide are extremely toxic molecules because they inhibit mitochondrial respiration. Curiously, NO, CO and H2S are also known gasotransmitters regulating the cardiovascular system as well as other processes such as inflammation.

    H2S is a source of electrons for a Sulfide Quinone Reductase (SQR) found in sulfo-oxidant bacteria and in mitochondria. H2S is consumed avidly by most mitochondria when present at nM to µM concentration and preferably to any other organic molecule. These characteristics avoid H2S accumulation and poisoning.

    Our main objective is to address the role of the mitochondrial sulfide oxidation pathway in physiological as well as in pathological states. Two very different situations are studied. The first is related to sulfide toxicity. It is essentially encountered in gut because of the sulfo-reductant bacteria of the microbiota. There the question is whether overwhelming the anti-sulfide defense of the gut has deleterious consequences such as inflammation, DNA damage, cancer. The second situation deals with the relationships between sulfide signaling and oxidation, which is modulated in most tissues by SQR.

    The group

    Abbas Abou-Hamdan (postdoc), Hala Guedouari-Bounihi (IE CDD), Nada Helmy (MD Ph D student).


    Research interests


    In collaboration with the group of F. Blachier (AgroParisTech) we showed that sulfide oxidation pathway is almost ubiquitous. It is obviously highly represented in colonic tissues. It is present in most tissues and cultured cells but, notably, absent in brain tissues and neuroblastoma cell lines. Furthermore we demonstrated that sulfide oxidation occurs at low micromolar concentration and takes precedence over other respiratory substrates
    (Biochim Biophys Acta. 2010 Aug;1797(8):1500-11Nitric Oxide. 2014 Sep 15;41:105-12.)

    We evidenced that the amount of respiratory chain complexes, and not that of the sulfide oxidation pathway, is the determinant factor for the enhanced sulfide tolerance of colonic cells upon their differentiation( Antioxid Redox Signal. 2012 Jul 1;17(1):1-10)

    We reviewed the data that support the overlap between toxic/trophic and signaling effect of sulfide (Br J Pharmacol. 2014 Apr;171(8):2099-122). In that context, we recently showed that the sulfide oxidation capacity of human liver can greatly vary. We evaluated its relevance to the individual blood pressure maintenance (Nitric Oxide. 2014 Sep 15;41:105-12)





     Main publications

    Haouzi P, Gueguinou M, Sonobe T, Judenherc-Haouzi A, Tubbs N, Trebak M, Cheung J, Bouillaud F. Revisiting the physiological effects of methylene blue as a treatment of cyanide intoxication. Clin Toxicol (Phila). 2018 56:828-840

    Touat M, Sourisseau T, Dorvault N, Chabanon RM, Garrido M, Morel D, Krastev DB, Bigot L, Adam J, Frankum JR, Durand S, Pontoizeau C, Souquère S, Kuo MS, Sauvaigo S, Mardakheh F, Sarasin A, Olaussen KA, Friboulet L, Bouillaud F, Pierron G, Ashworth A, Lombès A, Lord CJ, Soria JC, Postel-Vinay S. DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade. J Clin Invest. 2018 128:1671-1687.

    Šarić A, Crnolatac I, Bouillaud F, Sobočanec S, Mikecin AM, Mačak Šafranko Ž, Delgeorgiev T, Piantanida I, Balog T, Petit PX. Non-toxic fluorescent phosphonium probes to detect mitochondrial potential. Methods Appl Fluoresc. 2017 5:0150

    Poulain L, Sujobert P, Zylbersztejn F, Barreau S, Stuani L, Lambert M, Palama TL, Chesnais V, Birsen R, Vergez F, Farge T, Chenevier-Gobeaux C, Fraisse M, Bouillaud F, Debeissat C, Herault O, Récher C, Lacombe C, Fontenay M, Mayeux P, Maciel TT, Portais JC, Sarry JE, Tamburini J, Bouscary D, Chapuis N. High mTORC1 activity drives glycolysis addiction and sensitivity to G6PD inhibition in acute myeloid leukemia cells. Leukemia. 2017 31:2326-2335.

    Lorenz C, Lesimple P, Bukowiecki R, Zink A, Inak G, Mlody B, Singh M, Semtner M, Mah N, Auré K, Leong M, Zabiegalov O, Lyras EM, Pfiffer V, Fauler B, Eichhorst J, Wiesner B, Huebner N, Priller J, Mielke T, Meierhofer D, Izsvák Z, Meier JC, Bouillaud F, Adjaye J, Schuelke M, Wanker EE, Lombès A, Prigione A. Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders. Cell Stem Cell. 2017 20:659-674.e9.

    Wilson JL, Bouillaud F, Almeida AS, Vieira HL, Ouidja MO, Dubois-Randé JL, Foresti R, Motterlini R. Carbon monoxide reverses the metabolic adaptation of microglia cells to an inflammatory stimulus. Free Radic Biol Med. 2017104:311-323.

    Haidar M, Lombès A, Bouillaud F, Kennedy EJ, Langsley G. HK2 Recruitment to Phospho-BAD Prevents Its Degradation, Promoting Warburg Glycolysis by Theileria-Transformed Leukocytes. ACS Infect Dis. 2017 3:216-224

    Ohayon D, De Chiara A, Chapuis N, Candalh C, Mocek J, Ribeil JA, Haddaoui L, Ifrah N, Hermine O, Bouillaud F, Frachet P, Bouscary D, Witko-Sarsat V. Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia. Sci Rep. 2016 6:35561

    Vavrova E, Lenoir V, Alves-Guerra MC, Denis RG, Castel J, Esnous C, Dyck JR, Luquet S, Metzger D, Bouillaud F, Prip-Buus C. Muscle expression of a malonyl-CoA-insensitive carnitine palmitoyltransferase-1 protects mice against high-fat/high-sucrose diet-induced insulin resistance. Am J Physiol Endocrinol Metab. 2016 311:E649-60.

    Abou-Hamdan A, Ransy C, Roger T, Guedouari-Bounihi H, Galardon E, Bouillaud F. Positive feedback during sulfide oxidation fine-tunes cellular affinity for oxygen. Biochim Biophys Acta. 2016 1857:1464-1472.

    Bouillaud F, Alves-Guerra MC, Ricquier D. UCPs, at the interface between bioenergetics and metabolism. Biochim Biophys Acta. 2016 Oct;1863(10):2443-56

    Beaumont M, Andriamihaja M, Lan A, Khodorova N, Audebert M, Blouin JM, Grauso M, Lancha L, Benetti PH, Benamouzig R, Tomé D, Bouillaud F, Davila AM, Blachier F. Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response. Free Radic Biol Med. 2016 93:155-64

    Aït-Ali N, Fridlich R, Millet-Puel G, Clérin E, Delalande F, Jaillard C, Blond F, Perrocheau L, Reichman S, Byrne LC, Olivier-Bandini A, Bellalou J, Moyse E, Bouillaud F, Nicol X, Dalkara D, van Dorsselaer A, Sahel JA, Léveillard T. Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis. Cell. 2015 161:817-32

    Abou-Hamdan A, Guedouari-Bounihi H, Lenoir V, Andriamihaja M, Blachier F, Bouillaud F. Oxidation of H2S in mammalian cells and mitochondria. Methods Enzymol. 2015;554:201-28.

    Hénique C, Mansouri A, Vavrova E, Lenoir V, Ferry A, Esnous C, Ramond E, Girard J, Bouillaud F, Prip-Buus C, Cohen I. Increasing mitochondrial muscle fatty acid oxidation induces skeletal muscle remodeling toward an oxidative phenotype FASEB J. 2015 29:2473-83.

    Metheni M, Lombès A, Bouillaud F, Batteux F, Langsley G. HIF-1α induction, proliferation and glycolysis of Theileria-infected leukocytes. Cell Microbiol. 2015 17:467-72



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