Impact of Hydrogen Sulfide on Mitochondrial and Bacterial Bioenergetics.

Vitaliy B Borisov,Elena Forte

doi:10.3390/ijms222312688

Abstract

This review focuses on the effects of hydrogen sulfide (H2S) on the unique bioenergetic molecular machines in mitochondria and bacteria—the protein complexes of electron transport chains and associated enzymes. H2S, along with nitric oxide and carbon monoxide, belongs to the class of endogenous gaseous signaling molecules. This compound plays critical roles in physiology and pathophysiology. Enzymes implicated in H2S metabolism and physiological actions are promising targets for novel pharmaceutical agents. The biological effects of H2S are biphasic, changing from cytoprotection to cytotoxicity through increasing the compound concentration. In mammals, H2S enhances the activity of FoF1-ATP (adenosine triphosphate) synthase and lactate dehydrogenase via their S-sulfhydration, thereby stimulating mitochondrial electron transport. H2S serves as an electron donor for the mitochondrial respiratory chain via sulfide quinone oxidoreductase and cytochrome c oxidase at low H2S levels. The latter enzyme is inhibited by high H2S concentrations, resulting in the reversible inhibition of electron transport and ATP production in mitochondria. In the branched respiratory chain of Escherichia coli, H2S inhibits the bo3 terminal oxidase but does not affect the alternative bd-type oxidases. Thus, in E. coli and presumably other bacteria, cytochrome bd permits respiration and cell growth in H2S-rich environments. A complete picture of the impact of H2S on bioenergetics is lacking, but this field is fast-moving, and active ongoing research on this topic will likely shed light on additional, yet unknown biological effects.

Highlights

For a long time, hydrogen sulfide (H2S) had been considered merely as a highly toxic and occasionally lethal gas
H2S is considered to be a member of the class of gasotransmitters or, in other words, endogenous gaseous signaling molecules, along with nitric oxide and carbon monoxide [3–7]
This review focuses on the effects of H2S on the respiratory chains of mammalian m2.itEonchdoongderinaoaunds bParcotderuiac,tmioanmomfaHlia2nSFoF1-ATP synthase, and mammalian lactate dehydrogenInasmeainlialinghttisosfureecse,nHt fi2Sndcianngsb. e endogenously produced via both non-enzym

Summary

Introduction

Hydrogen sulfide (H2S) had been considered merely as a highly toxic and occasionally lethal gas. H2S contributes to the regulation of important physiological processes in the cardiovascular, gastrointestinal, nervous, and respiratory systems It shows various physiological effects in mammalian cells, but in a biphasic, concentration-dependent manner. H2S exerts vasorelaxant effects through the opening of KATP (adenosine triphosphate) channels in vascular smooth muscle cells [9] It functions as a neuromodulator in the brain [1] and serves as a stimulator of angiogenesis [10]. At concentrations of 200 μM and higher, H2S induces apoptosis of aorta smooth muscle cells through the activation of mitogen-activated protein kinases and caspase-3 [11]. H2O2 into H2O; (ii) depletion of Fe2+, a catalyst of the Fenton reaction; (iii) transien tion of free cysteine, a reducing agent that fuels the Fenton reaction; and (iv) stim of the activities of superoxide dismutase (SOD) and catalase [15] The latter two e are the well-known ROS scavenging systems [16]. It is a weak acid; in aqueous solutio equilibrates with hydrosulfide (HS−) and sulfide (S2−) according to Equati3oonf 1(91):

H S HS H

Enzymatic

S-Sulfhydration of ATP Synthase

Findings

H2S at Toxic Concentrations Inhibits Mitochondrial Cytochrome c Oxidase