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Cytochrome c Reduction by H2S Potentiates Sulfide Signaling.

Abstract：

:Hydrogen sulfide (H2S) 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 H2S has been reported previously but not characterized. In this study, we demonstrate that reduction of ferric Cyt C by H2S 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 H2S oxidized. H2S increases O2 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 H2S 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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Vitvitsky V,Miljkovic JL,Bostelaar T,Adhikari B,Yadav PK,Steiger AK,Torregrossa R,Pluth MD,Whiteman M,Banerjee R,Filipovic MR

doi

10.1021/acschembio.8b00463

subject

Has Abstract

pub_date

2018-08-17 00:00:00

pages

2300-2307

issue

8

eissn

1554-8929

issn

1554-8937

journal_volume

13

pub_type

杂志文章

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