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Cytochrome c Reduction by HS Potentiates Sulfide Signaling. | LitMetric

AI Article Synopsis

Article Abstract

Hydrogen sulfide (HS) is an endogenously produced gas that is toxic at high concentrations. It is eliminated by a dedicated mitochondrial sulfide oxidation pathway, which connects to the electron transfer chain at the level of complex III. Direct reduction of cytochrome c (Cyt C) by HS has been reported previously but not characterized. In this study, we demonstrate that reduction of ferric Cyt C by HS exhibits hysteretic behavior, which suggests the involvement of reactive sulfur species in the reduction process and is consistent with a reaction stoichiometry of 1.5 mol of Cyt C reduced/mol of HS oxidized. HS increases O consumption by human cells (HT29 and HepG2) treated with the complex III inhibitor antimycin A, which is consistent with the entry of sulfide-derived electrons at the level of complex IV. Cyt C-dependent HS oxidation stimulated protein persulfidation in vitro, while silencing of Cyt C expression decreased mitochondrial protein persulfidation in a cell culture. Cyt C released during apoptosis was correlated with persulfidation of procaspase 9 and with loss of its activity. These results reveal a potential role for the electron transfer chain in general, and Cyt C in particular, for potentiating sulfide-based signaling.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450078PMC
http://dx.doi.org/10.1021/acschembio.8b00463DOI Listing

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