Oxidation of hydrogen sulfide remains a priority in mammalian cells and causes reverse electron transfer in colonocytes.
Sulfide (H2S) is an inhibitor of mitochondrial cytochrome oxidase comparable to cyanide. In this study, poisoning of cells was observed with sulfide concentrations above 20 microM. Sulfide oxidation has been shown to take place in organisms/cells naturally exposed to sulfide. Sulfide is released as a result of metabolism of sulfur containing amino acids. Although in mammals sulfide exposure is not thought to be quantitatively important outside the colonic mucosa, our study shows that a majority of mammalian cells, by means of the mitochondrial sulfide quinone reductase (SQR), avidly consume sulfide as a fuel. The SQR activity was found in mitochondria isolated from mouse kidneys, liver, and heart. We demonstrate the precedence of the SQR over the mitochondrial complex I. This explains why the oxidation of the mineral substrate sulfide takes precedence over the oxidation of other (carbon-based) mitochondrial substrates. Consequently, if sulfide delivery rate remains lower than the SQR activity, cells maintain a non-toxic sulfide concentration (<1 microM) in their external environment. In the colonocyte cell line HT-29, sulfide oxidation provided the first example of reverse electron transfer in living cells, such a transfer increasing sulfide tolerance. However, SQR activity was not detected in brain mitochondria and neuroblastoma cells. Consequently, the neural tissue would be more sensitive to sulfide poisoning. Our data disclose new constraints concerning the emerging signaling role of sulfide.
Lagoutte
Emilie
E
CNRS-FRE3210, Université René Descartes, Site Necker 156 rue de Vaugirard, 75730 Paris cedex15, France.
Mimoun
Sabria
S
Andriamihaja
Mireille
M
Chaumontet
Catherine
C
Blachier
François
F
Bouillaud
Frédéric
F
D000818:Animals; D016466:CHO Cells; D003106:Colon / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004579:Electron Transport; D019073:HT29 Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011808:Quinone Reductases / Q000235:genetics / Q000502:physiology; D012402:Rotenone / Q000494:pharmacology; D015398:Signal Transduction
D012402:Rotenone; D009243:NAD; D011808:Quinone Reductases; C073412:sulfide quinone reductase; D006862:Hydrogen Sulfide