Kumar 2021 J Biol Chem

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Kumar R, Landry AP, Guha A, Vitvitsky V, Lee HJ, Seike K, Reddy P, Lyssiotis CA, Banerjee R (2021) A redox cycle with complex II prioritizes sulfide quinone oxidoreductase dependent H2S oxidation. J Biol Chem 298:101435.

» PMID: 34808207 Open Access

Kumar Roshan, Landry Aaron P, Guha Arkajit, Vitvitsky Victor, Lee Ho Joon, Seike Keisuke, Reddy Pavan, Lyssiotis Costas A, Banerjee Ruma (2021) J Biol Chem

Abstract: The dual roles of H2S as an endogenously synthesized respiratory substrate and as a toxin, raise questions as to how it is cleared when the electron transport chain is inhibited. Sulfide quinone oxidoreductase (SQOR) catalyzes the first step in the mitochondrial H2S oxidation pathway, using CoQ as an electron acceptor, and connects to the electron transport chain at the level of complex III. We have discovered that at high H2S concentrations, which are known to inhibit complex IV, a new redox cycle is established between SQOR and complex II, operating in reverse. Under these conditions, the purine nucleotide cycle and the malate aspartate shuttle furnish fumarate, which supports complex II reversal and leads to succinate accumulation. Complex II knockdown in colonocytes decreases the efficiency of H2S clearance while targeted knockout of complex II in intestinal epithelial cells significantly decreases the levels of thiosulfate, a biomarker of H2S oxidation, to approximately one third of the values seen in serum and urine samples from control mice. These data establish the physiological relevance of this newly discovered redox circuitry between SQOR and complex II for prioritizing H2S oxidation and reveal the quantitatively significant contribution of intestinal epithelial cells to systemic H2S metabolism. Keywords: SDHA, Coenzyme Q, Complex II, Electron transport chain, Fumarate, Hydrogen sulfide Bioblast editor: Plangger M

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell  Preparation: Intact cells  Enzyme: Complex II;succinate dehydrogenase 

HRR: Oxygraph-2k