Sulfide Oxidation Pathway Research Articles

Essential role of sulfide oxidation in brain health and neurological disorders.

Hydrogen sulfide (H2S) is an environmental hazard well known for its neurotoxicity. In mammalian cells, H2S is predominantly generated by transsulfuration pathway enzymes. In addition, H2S produced by gut microbiome significantly contributes to the total sulfide burden in the body. Although low levels of H2S is believed to exert various physiological functions such as neurotransmission and vasomotor control, elevated levels of H2S inhibit the activity of cytochrome c oxidase (i.e., mitochondrial complex IV), thereby impairing oxidative phosphorylation. To protect the electron transport chain from respiratory poisoning by H2S, the compound is actively oxidized to form persulfides and polysulfides by a mitochondrial resident sulfide oxidation pathway. The reaction, catalyzed by sulfide:quinone oxidoreductase (SQOR), is the initial and critical step in sulfide oxidation. The persulfide species are subsequently oxidized to sulfite, thiosulfate, and sulfate by persulfide dioxygenase (ETHE1 or SDO), thiosulfate sulfurtransferase (TST), and sulfite oxidase (SUOX). While SQOR is abundantly expressed in the colon, liver, lung, and skeletal muscle, its expression is notably low in the brains of most mammals. Consequently, the brain's limited capacity to oxidize H2S renders it particularly sensitive to the deleterious effects of H2S accumulation. Impaired sulfide oxidation can lead to fatal encephalopathy, and the overproduction of H2S has been implicated in the developmental delays observed in Down syndrome. Our recent findings indicate that the brain's limited capacity to oxidize sulfide exacerbates its sensitivity to oxygen deprivation. The beneficial effects of sulfide oxidation are likely to be mediated not only by the detoxification of H2S but also by the formation of persulfide, which exerts cytoprotective effects through multiple mechanisms. Therefore, pharmacological agents designed to scavenge H2S and/or enhance persulfide levels may offer therapeutic potential against neurological disorders characterized by impaired or insufficient sulfide oxidation or excessive H2S production.

Advanced methanotrophic bioreactor design for efficient bioremediation of hydrogen sulfide (H₂S) And Volatile Organic Compounds (Vocs): Integrating genetic engineering and industrial scalability

The convergence of advanced microbial biotechnology and metabolic engineering has facilitated groundbreaking advancements in bioremediation. This study presents the engineered Methylomicrobium buryatense strain 5GB1C-RO1, optimized for the simultaneous removal of hydrogen sulfide (H₂S) and volatile organic compounds (VOCs) within a two-stage methanotrophic bioreactor system. Through precise CRISPR/Cas9-mediated genome editing, critical metabolic pathways for sulfide oxidation (SQR, FCCAB, SOXABXYZ) and VOC degradation (alkB, adhP, todC1C2BA) were integrated, achieving catalytic efficiencies exceeding 3.2 × 10⁷ M⁻¹s⁻¹ and substrate conversion rates above 450 nmol min⁻¹ mg⁻¹ protein. The strain demonstrates exceptional robustness under industrial conditions, maintaining 95% pollutant removal efficiency at H₂S concentrations up to 1000 ppm and VOC concentrations exceeding 500 ppm. The innovative bioreactor system incorporates enhanced gas-liquid mass transfer mechanisms, achieving mass transfer coefficients (kLa) exceeding 300 h⁻¹ and enabling stable operation for over 1000 continuous hours. Experimental results confirm the system's capacity for pollutant mineralization, generating methane-rich biogas (>95% CH₄) and high-protein microbial biomass (>85%), which are valuable for energy and agricultural applications. This integrated bioremediation approach not only reduces reliance on chemical scrubbing and flaring but also supports circular economy principles by transforming waste gases into renewable resources. The technology provides a scalable, sustainable, and cost-effective solution to mitigate industrial emissions while addressing environmental and regulatory challenges. The findings highlight the potential of combining advanced genetic engineering with innovative bioreactor design to redefine industrial pollutant management and resource recovery.

Production of a cellulose-aminating polysaccharide from a filamentous sulfur-oxidizing bacterium, Thiothrix nivea, grown lithotrophically or mixotrophically.

Glucosaminoglucan (β-1,4-linked glucose and glucosamine) produced by a mixotrophic sulfur-oxidizing bacterium, Thiothrix nivea, is a useful cellulose-aminating agent. Lithotrophic and mixotrophic glucosaminoglucan production were examined using fed-batch techniques. A jar fermenter was used for the fed-batch cultivation. Glucosaminoglucan was extracted from T. nivea using diluted HCl. Lithotrophic growth was detected by feeding with Na2S as the energy source, and 12mg L-culture-1 of glucosaminoglucan was obtained. In contrast, no growth was observed with Na2S2O3. Similarly, mixotrophic growth in the presence of acetic acid was promoted by Na2S, whereas Na2S2O3 had no effect. When acetic acid and Na2S were added, 470mg L-culture-1 of glucosaminoglucan was obtained. T. nivea was cultured and glucosaminoglucan was produced lithotrophically using Na2S for feeding. Na2S is also indispensable for mixotrophic growth and glucosaminoglucan production, indicating that sulfide oxidation pathways control the TCA cycle. The involvement of the SOX pathway (for thiosulfate oxidation) in the activation of energy metabolism is doubtful because neither lithotrophic nor mixotrophic growth was promoted by Na2S2O3. Based on these results, we assumed that T. nivea is facultatively mixotrophic (lithotrophic growth is possible in addition to organotrophic growth in the presence of sulfide (Na2S)), rather than obligately mixotrophic.

From microbial heterogeneity to evolutionary insights: A strain-resolved metagenomic study of H2S-induced changes in anaerobic biofilms

The hidden layers of genomic diversity in microbiota of biotechnological interest have been only partially explored and a deeper investigation that overcome species level resolution is needed. CO2-fixating microbiota are prone to such evaluation as case study. A lab-scale trickle-bed reactor was employed to successfully achieve simultaneous biomethanation and desulfurization on artificial biogas and sulfur-rich biogas, and oxygen supplementation was also implemented. Under microaerophilic conditions, hydrogen sulfide removal efficiency of 81% and methane content of 95% were achieved. Methanobacterium sp. DTU45 emerged as predominant, and its metabolic function was tied to community-wide dynamics in sulfur catabolism. Genomic evolution was investigated in Gammaproteobacteria sp. DTU53, identified as the main contributor to microaerophilic desulfurization. Positive selection of variants in the hydrogen sulfide oxidation pathway was discovered and amino acid variants were localized on the sulfide entrance channel for sulfide:quinone oxidoreductase. Upon oxygen supplementation strain selection was the primary mechanism driving microbial adaptation, rather than a shift in species dominance. Selective pressure determined the emergence of new strains for example on Gammaproteobacteria sp. DTU53, providing in depth evidence of functional redundancy within the microbiome.

A modelling method for simulating nitrogen dynamics under the hydrodynamic context of river network

River network comprised by varieties of interconnected rivers is an essential form of lotic environments. Unravelling the biogeochemical processes are essential for promoting the water quality and ecological health of river networks. However, biogeochemical processes in river networks are difficult to be quantified, since they are controlled by multi-directional mass transport processes and transformation processes associated with varieties of microbial metabolic pathways. To address this gap, the present research combined turbulence model and gene-centric model to establish a systematic modelling method to quantitively describe the nitrogen dynamics in a river network. The proposed model can capture the mass transport and microbial metabolic processes, and can accurately simulate the distribution characteristics of chemical materials and functional genes. The relative errors between simulated results and in-site measured data were low than 40%. With the help of the modelling method, this study further investigated the nitrogen dynamics in the river network. The results illustrated sulfide oxidation and nitrate reduction pathway and anaerobic ammonium oxidation pathway, participated by genes hzo and nap respectively, were the main pathways of NO3– and NO2– reduction. Besides, these two pathways exhibited high rates in all of the six confluence hydrodynamic zones (CHZs) of the river network and further increased the nitrogen removal efficiency. Moreover, the high-rate nitrogen removal processes continued in the downstream areas after CHZs, and the scope of such continuous influences increased with the discharge ratio between tributary and main stream. The modelling method and results in this research can be useful for prediction of water environmental quality and design of river connection engineering.

Enhancing the bioavailability of sulfur for denitrification in integrated floating-film and activated sludge (IFFAS) system filled with modified carriers under mixotrophic and autotrophic conditions

Sulfur autotrophic denitrification (SAD) holds application prospect in carbon-limited wastewater due to no additional carbon source, less sludge yield, and lower costs. However, the poor bioavailability of sulfur (S0) and the slow development of sulfur oxidizing bacteria (SOB) limit its wide application. Tween 80 is a nonionic surfactant with low toxicity and can regulate interface action between S0 and microorganisms. In this study, integrated floating-film and activated sludge (IFFAS) filled with graphene oxide (GO)-modified carriers was adopted and Tween 80 was introduced to enhance bioavailability of S0. When the influent C/N was below 0.7 and nitrogen loading was 0.24 Kg/(m3∙d), the total nitrogen removal efficiencies in reactors filled with GO-modified carriers and Tween 80 were above 90% while that of reactors filled with high density polyethylene (HDPE) carriers and 0.5 wt% GO-modified carriers was74.08 ± 12.8% and 81.87 ± 11.51%. Microbial analysis revealed that Tween 80 could enhance autotrophic denitrification bacteria relative abundance in biofilm at C/N ratios of < 0.7, such as Sulfurisoma (21.21%), Dechloromonas (8.42%) and Ignavibacterium (14.68%). Furthermore, predicted microbial functions analysis by PICRUSt showed that denitrification, sulfide oxidation, electron transfer and biofilm formation pathways were enhanced in reactors added Tween 80. This study demonstrated Tween 80 was able to improve the bioavailability of S0 and enhance the efficiency of SAD.

Temperature and pH on microbial desulfurization of sulfide wastewater: From removal performance to gene regulation mechanism

Sulfides are widely present in industrial wastewater cause environmental problems like malodorous, corrosive, and toxic. Microbial desulfurization technology has the advantages of ambient conditions, low energy consumption, and enables the recovery of sulfur (S0). These advantages make it the technology of choice for treating middle and low loads of sulfide wastewater. Temperature and pH are two important factors that affect the product selectivity of microbial desulfurization, but the mechanism of these two factors regulating the genes and metabolic pathways of functional microorganisms remains unclear. In this study, a sequencing batch reactor (SBR) treated sulfide-containing wastewater, achieving complete degradation of 400 mg/L influent sulfide at 30 °C and pH 7.5 and showed the best S0 formation efficiency (91.1 ± 2.1 %). The Halothiobacillus genus dominated the microbial community, with the highest abundance (73.0 %) at 30 °C and pH 7.5. Metagenomic analysis showed that at 30 °C and pH 7.5 compared with 20 °C or pH 6.5, the abundance of sulfide oxidation genes (sqr, fccAB) were significantly increased (49.9 % and 43.0 %, 1303.3 % and 139.4 %). Under unfavorable temperature and pH, fccAB gene abundance decreased significantly (92.9 %, 58.2 %), sqr decreased less (33.3 %, 30.1 %), and sox increased significantly (241.0 %, 122.1 %). The dominate sulfide oxidation pathway from flavocytochrome c (FCC) shifted to the sulfide: quinone oxidoreductase (SQR) and sulfur oxidizing system (SOX) pathways. This work highlights the ability of modulating temperature and pH to optimize the biological treatment of sulfide-containing wastewater processes and obtaining more S0, and elucidates their effects on metabolic pathways associated with sulfide oxidation.

Complexities of complex II: Sulfide metabolism in vivo

High levels of H2S produced by gut microbiota can block oxygen utilization by inhibiting mitochondrial complex IV. Kumar et al. have shown how cells respond to this inhibition by using the mitochondrial sulfide oxidation pathway and reverse electron transport. The reverse activity of mitochondrial complex II (succinate-quinone oxidoreductase, i.e., fumarate reduction) generates oxidized coenzyme Q, which is then reduced by the mitochondrial sulfide quinone oxidoreductase to oxidize H2S. This newly identified redox circuitry points to the importance of complex II reversal in mitochondria during periods of hypoxia and cellular stress.

The Pathway of Sulfide Oxidation to Octasulfur Globules in the Cytoplasm of Aerobic Bacteria.

Sulfur-oxidizing bacteria can oxidize hydrogen sulfide (H2S) to produce sulfur globules. Although the process is common, the pathway is unclear. In recombinant Escherichia coli and wild-type Corynebacterium vitaeruminis DSM 20294 with sulfide:quinone oxidoreductase (SQR) but no enzymes to oxidize zero valence sulfur, SQR oxidized H2S into short-chain inorganic polysulfide (H2Sn, n ≥ 2) and organic polysulfide (RSnH, n ≥ 2), which reacted with each other to form long-chain GSnH (n ≥ 2) and H2Sn before producing octasulfur (S8), the main component of elemental sulfur. GSnH also reacted with glutathione (GSH) to form GSnG (n ≥ 2) and H2S; H2S was again oxidized by SQR. After GSH was depleted, SQR simply oxidized H2S to H2Sn, which spontaneously generated S8. S8 aggregated into sulfur globules in the cytoplasm. The results highlight the process of sulfide oxidation to S8 globules in the bacterial cytoplasm and demonstrate the potential of using heterotrophic bacteria with SQR to convert toxic H2S into relatively benign S8 globules. IMPORTANCE Our results provide evidence of H2S oxidation producing octasulfur globules via sulfide:quinone oxidoreductase (SQR) catalysis and spontaneous reactions in the bacterial cytoplasm. Since the process is an important event in geochemical cycling, a better understanding facilitates further studies and provides theoretical support for using heterotrophic bacteria with SQR to oxidize toxic H2S into sulfur globules for recovery.

The hepatic compensatory response to elevated systemic sulfide promotes diabetes.

SummaryImpaired hepatic glucose and lipid metabolism are hallmarks of type 2 diabetes. Increased sulfide production or sulfide donor compounds may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range. We show that mice lacking the liver- enriched mitochondrial SOP enzyme thiosulfate sulfurtransferase (Tst−/− mice) exhibit high circulating sulfide, increased gluconeogenesis, hypertriglyceridemia, and fatty liver. Unexpectedly, hepatic sulfide levels are normal in Tst−/− mice because of exaggerated induction of sulfide disposal, with associated suppression of global protein persulfidation and nuclear respiratory factor 2 target protein levels. Hepatic proteomic and persulfidomic profiles converge on gluconeogenesis and lipid metabolism, revealing a selective deficit in medium-chain fatty acid oxidation in Tst−/− mice. We reveal a critical role of TST in hepatic metabolism that has implications for sulfide donor strategies in the context of metabolic disease.

Revealing the full biosphere structure and versatile metabolic functions in the deepest ocean sediment of the Challenger Deep

BackgroundThe full biosphere structure and functional exploration of the microbial communities of the Challenger Deep of the Mariana Trench, the deepest known hadal zone on Earth, lag far behind that of other marine realms.ResultsWe adopt a deep metagenomics approach to investigate the microbiome in the sediment of Challenger Deep, Mariana Trench. We construct 178 metagenome-assembled genomes (MAGs) representing 26 phyla, 16 of which are reported from hadal sediment for the first time. Based on the MAGs, we find the microbial community functions are marked by enrichment and prevalence of mixotrophy and facultative anaerobic metabolism. The microeukaryotic community is found to be dominated by six fungal groups that are characterized for the first time in hadal sediment to possess the assimilatory and dissimilatory nitrate/sulfate reduction, and hydrogen sulfide oxidation pathways. By metaviromic analysis, we reveal novel hadal Caudovirales clades, distinctive virus-host interactions, and specialized auxiliary metabolic genes for modulating hosts’ nitrogen/sulfur metabolism. The hadal microbiome is further investigated by large-scale cultivation that cataloged 1070 bacterial and 19 fungal isolates from the Challenger Deep sediment, many of which are found to be new species specialized in the hadal habitat.ConclusionOur hadal MAGs and isolates increase the diversity of the Challenger Deep sediment microbial genomes and isolates present in the public. The deep metagenomics approach fills the knowledge gaps in structure and diversity of the hadal microbiome, and provides novel insight into the ecology and metabolism of eukaryotic and viral components in the deepest biosphere on earth.

Metaproteogenomic Profiling of Chemosynthetic Microbial Biofilms Reveals Metabolic Flexibility During Colonization of a Shallow-Water Gas Vent.

Tor Caldara is a shallow-water gas vent located in the Mediterranean Sea, with active venting of CO2 and H2S. At Tor Caldara, filamentous microbial biofilms, mainly composed of Epsilon- and Gammaproteobacteria, grow on substrates exposed to the gas venting. In this study, we took a metaproteogenomic approach to identify the metabolic potential and in situ expression of central metabolic pathways at two stages of biofilm maturation. Our findings indicate that inorganic reduced sulfur species are the main electron donors and CO2 the main carbon source for the filamentous biofilms, which conserve energy by oxygen and nitrate respiration, fix dinitrogen gas and detoxify heavy metals. Three metagenome-assembled genomes (MAGs), representative of key members in the biofilm community, were also recovered. Metaproteomic data show that metabolically active chemoautotrophic sulfide-oxidizing members of the Epsilonproteobacteria dominated the young microbial biofilms, while Gammaproteobacteria become prevalent in the established community. The co-expression of different pathways for sulfide oxidation by these two classes of bacteria suggests exposure to different sulfide concentrations within the biofilms, as well as fine-tuned adaptations of the enzymatic complexes. Taken together, our findings demonstrate a shift in the taxonomic composition and associated metabolic activity of these biofilms in the course of the colonization process.

Genomic evidence for sulfur intermediates as new biogeochemical hubs in a model aquatic microbial ecosystem

BackgroundThe sulfur cycle encompasses a series of complex aerobic and anaerobic transformations of S-containing molecules and plays a fundamental role in cellular and ecosystem-level processes, influencing biological carbon transfers and other biogeochemical cycles. Despite their importance, the microbial communities and metabolic pathways involved in these transformations remain poorly understood, especially for inorganic sulfur compounds of intermediate oxidation states (thiosulfate, tetrathionate, sulfite, polysulfides). Isolated and highly stratified, the extreme geochemical and environmental features of meromictic ice-capped Lake A, in the Canadian High Arctic, provided an ideal model ecosystem to resolve the distribution and metabolism of aquatic sulfur cycling microorganisms along redox and salinity gradients.ResultsApplying complementary molecular approaches, we identified sharply contrasting microbial communities and metabolic potentials among the markedly distinct water layers of Lake A, with similarities to diverse fresh, brackish and saline water microbiomes. Sulfur cycling genes were abundant at all depths and covaried with bacterial abundance. Genes for oxidative processes occurred in samples from the oxic freshwater layers, reductive reactions in the anoxic and sulfidic bottom waters and genes for both transformations at the chemocline. Up to 154 different genomic bins with potential for sulfur transformation were recovered, revealing a panoply of taxonomically diverse microorganisms with complex metabolic pathways for biogeochemical sulfur reactions. Genes for the utilization of sulfur cycle intermediates were widespread throughout the water column, co-occurring with sulfate reduction or sulfide oxidation pathways. The genomic bin composition suggested that in addition to chemical oxidation, these intermediate sulfur compounds were likely produced by the predominant sulfur chemo- and photo-oxidisers at the chemocline and by diverse microbial degraders of organic sulfur molecules.ConclusionsThe Lake A microbial ecosystem provided an ideal opportunity to identify new features of the biogeochemical sulfur cycle. Our detailed metagenomic analyses across the broad physico-chemical gradients of this permanently stratified lake extend the known diversity of microorganisms involved in sulfur transformations over a wide range of environmental conditions. The results indicate that sulfur cycle intermediates and organic sulfur molecules are major sources of electron donors and acceptors for aquatic and sedimentary microbial communities in association with the classical sulfur cycle.-hYdWkMRSgNRZXNRu4CdmLVideo abstract

Time series metagenomic sampling of the Thermopyles, Greece, geothermal springs reveals stable microbial communities dominated by novel sulfur-oxidizing chemoautotrophs.

Geothermal springs are essentially unaffected by environmental conditions aboveground as they are continuously supplied with subsurface water with little variability in chemistry. Therefore, changes in their microbial community composition and function, especially over a long period, are expected to be limited but this assumption has not yet been rigorously tested. Toward closing this knowledge gap, we applied whole metagenome sequencing to 17 water samples collected between 2010 and 2016 from the Thermopyles sulfur-rich geothermal springs in central Greece. As revealed by 16S rRNA gene fragments recovered in the metagenomes, Epsilonproteobacteria-related operational taxonomic units (OTUs) dominated most samples and grouping of samples based on OTU abundances exhibited no apparent seasonal pattern. Similarities between samples regarding functional gene content were high, with all samples sharing >70% similarity in functional pathways. These community-wide patterns were further confirmed by analysis of metagenome-assembled genomes (MAGs), which showed that novel species and genera of the chemoautotrophic Campylobacterales order dominated the springs. These MAGs carried different pathways for thiosulfate or sulfide oxidation coupled to carbon fixation pathways. Overall, our study showed that even in the long term, functions of microbial communities in a moderately hot terrestrial spring remain stable, presumably driving the corresponding stability in community structure.

Hydrogen Sulfide Oxidation by Sulfide Quinone Oxidoreductase.

Hydrogen sulfide (H2 S) is an environmental toxin and a heritage of ancient microbial metabolism that has stimulated new interest following its discovery as a neuromodulator. While many physiological responses have been attributed to low H2 S levels, higher levels inhibit complex IV in the electron transport chain. To prevent respiratory poisoning, a dedicated set of enzymes that make up the mitochondrial sulfide oxidation pathway exists to clear H2 S. The committed step in this pathway is catalyzed by sulfide quinone oxidoreductase (SQOR), which couples sulfide oxidation to coenzyme Q10 reduction in the electron transport chain. The SQOR reaction prevents H2 S accumulation and generates highly reactive persulfide species as products; these can be further oxidized or can modify cysteine residues in proteins by persulfidation. Here, we review the kinetic and structural characteristics of human SQOR, and how its unconventional redox cofactor configuration and substrate promiscuity lead to sulfide clearance and potentially expand the signaling potential of H2 S. This dual role of SQOR makes it a promising target for H2 S-based therapeutics.

The Heterotrophic Bacterium Cupriavidus pinatubonensis JMP134 Oxidizes Sulfide to Sulfate with Thiosulfate as a Key Intermediate.

Heterotrophic bacteria actively participate in the biogeochemical cycle of sulfur on Earth. The heterotrophic bacterium Cupriavidus pinatubonensis JMP134 contains several enzymes involved in sulfur oxidation, but how these enzymes work together to oxidize sulfide in the bacterium has not been studied. Using gene-deletion and whole-cell assays, we determined that the bacterium uses sulfide:quinone oxidoreductase to oxidize sulfide to polysulfide, which is further oxidized to sulfite by persulfide dioxygenase. Sulfite spontaneously reacts with polysulfide to produce thiosulfate. The sulfur-oxidizing (Sox) system oxidizes thiosulfate to sulfate. Flavocytochrome c sulfide dehydrogenase enhances thiosulfate oxidation by the Sox system but couples with the Sox system for sulfide oxidation to sulfate in the absence of sulfide:quinone oxidoreductase. Thus, C. pinatubonensis JMP134 contains a main pathway and a contingent pathway for sulfide oxidation.IMPORTANCE We establish a new pathway of sulfide oxidation with thiosulfate as a key intermediate in Cupriavidus pinatubonensis JMP134. The bacterium mainly oxidizes sulfide by using sulfide:quinone oxidoreductase, persulfide dioxygenase, and the Sox system with thiosulfate as a key intermediate. Although the purified and reconstituted Sox system oxidizes sulfide, its rate of sulfide oxidation in C. pinatubonensis JMP134 is too low to be physiologically relevant. The findings reveal how these sulfur-oxidizing enzymes participate in sulfide oxidation in a single bacterium.

Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolism.

Abnormalities of one carbon, glutathione and sulfide metabolisms have recently emerged as novel pathomechanisms in diseases with mitochondrial dysfunction. However, the mechanisms underlying these abnormalities are not clear. Also, we recently showed that sulfide oxidation is impaired in Coenzyme Q10 (CoQ10) deficiency. This finding leads us to hypothesize that the therapeutic effects of CoQ10, frequently administered to patients with primary or secondary mitochondrial dysfunction, might be due to its function as cofactor for sulfide:quinone oxidoreductase (SQOR), the first enzyme in the sulfide oxidation pathway. Here, using biased and unbiased approaches, we show that supraphysiological levels of CoQ10 induces an increase in the expression of SQOR in skin fibroblasts from control subjects and patients with mutations in Complex I subunits genes or CoQ biosynthetic genes. This increase of SQOR induces the downregulation of the cystathionine β-synthase and cystathionine γ-lyase, two enzymes of the transsulfuration pathway, the subsequent downregulation of serine biosynthesis and the adaptation of other sulfide linked pathways, such as folate cycle, nucleotides metabolism and glutathione system. These metabolic changes are independent of the presence of sulfur aminoacids, are confirmed in mouse models, and are recapitulated by overexpression of SQOR, further proving that the metabolic effects of CoQ10 supplementation are mediated by the overexpression of SQOR. Our results contribute to a better understanding of how sulfide metabolism is integrated in one carbon metabolism and may explain some of the benefits of CoQ10 supplementation observed in mitochondrial diseases.

Mechanisms of sulfur selection and sulfur secretion in a biological sulfide removal (BISURE) system

Biological desulfurization technology is a sustainable process for the sulfide removal from biogas, which has multiple advantages. In this study, a biological sulfide removal (BISURE) system was established to investigate the working performances and process mechanisms. The results showed that the sulfide removal rate was 2.30 kg-S/(m3 d), the sulfide removal efficiency was higher than 98%, the sulfur production rate was 1.76 kg-S/(m3 d), the sulfur selectivity was 75.02 ± 3.63% and the main form of products (sulfur compounds) was Rosickyite-S and S8. The performance of BISURE system was supported by the dominant genus (abundance more than 60%) of sulfur-oxidizing bacteria (SOB) which shifted to Thiovirga at the high SLR. The sqr and dsrA genes could serve as the indicators for the pathway of two-step sulfide oxidation, i.e. “partial sulfide oxidation (PSO, sulfide → sulfur)” and “complete sulfide oxidation (CSO, sulfur → sulfate)”. The sulfur selectivity was improved by enhancing PSO and inhibiting CSO with the indication of two genes. The cellular sulfur secretion was revealed, and the “outer-membrane vesicles (OMVs)-dependent” sulfur-secreting hypothesis was proposed to explain the transportation of elemental sulfur from inside to outside of SOB cells. The findings of this work provide a new perspective to understand the sulfur selection of sulfide bio-oxidation and the sulfur secretion of SOB cells so as to promote the development of biological desulfurization technology.

Hydrogen sulfide perturbs mitochondrial bioenergetics and triggers metabolic reprogramming in colon cells

Unlike most other tissues, the colon epithelium is exposed to high levels of H2S derived from gut microbial metabolism. H2S is a signaling molecule that modulates various physiological effects. It is also a respiratory toxin that inhibits complex IV in the electron transfer chain (ETC). Colon epithelial cells are adapted to high environmental H2S exposure as they harbor an efficient mitochondrial H2S oxidation pathway, which is dedicated to its disposal. Herein, we report that the sulfide oxidation pathway enzymes are apically localized in human colonic crypts at the host-microbiome interface, but that the normal apical-to-crypt gradient is lost in colorectal cancer epithelium. We found that sulfide quinone oxidoreductase (SQR), which catalyzes the committing step in the mitochondrial sulfide oxidation pathway and couples to complex III, is a critical respiratory shield against H2S poisoning. H2S at concentrations ≤20 μm stimulated the oxygen consumption rate in colon epithelial cells, but, when SQR expression was ablated, H2S concentrations as low as 5 μm poisoned cells. Mitochondrial H2S oxidation altered cellular bioenergetics, inducing a reductive shift in the NAD+/NADH redox couple. The consequent electron acceptor insufficiency caused uridine and aspartate deficiency and enhanced glutamine-dependent reductive carboxylation. The metabolomic signature of this H2S-induced stress response mapped, in part, to redox-sensitive nodes in central carbon metabolism. Colorectal cancer tissues and cell lines appeared to counter the growth-restricting effects of H2S by overexpressing sulfide oxidation pathway enzymes. Our findings reveal an alternative mechanism for H2S signaling, arising from alterations in mitochondrial bioenergetics that drive metabolic reprogramming.

Reprogramming of Colonic Cell Metabolism by H2S

Synthesis of H2S by gut microbiota leads to routine colonic cells exposure to this respiratory toxin. Herein we studied the effect of H2S on metabolism and proliferation in human colonic cells in culture at sulfide concentrations up to 300 μM, which represents a physiologically relevant exposure for these cells. H2S caused a marked activation of glycolysis and inhibition of proliferation. Between 5–20 μM H2S the oxygen consumption rate (OCR) was activated, while OCR was inhibited at higher concentrations. A high‐capacity mitochondrial sulfide oxidation pathway housed in colonocytes supports O2‐dependent H2S clearance and the absence of the committing enzyme (sulfide quinone reductase) in the pathway leads to inhibition of OCR even at the lowest H2S concentration that was tested. H2S triggers persulfidation of numerous protein targets that are enriched in energy metabolism pathways. The antiproliferative effect of H2S exposure results from electron acceptor insufficiency that ensues from H2S oxidation activity and inhibition of respiration. Under these conditions, reductive carboxylation of a‐ketoglutarate is enhanced and exogenous uridine and aspartate alleviated H2S‐imposed growth restriction. Overexpression of the sulfide oxidation enzymes in colon cancer tissue and cells confers a growth advantage during H2S exposure compared to non‐malignant cells. These results predict that the stress response in colonocytes triggered by microbial H2S exposure involves metabolic reprogramming to recycle electron acceptors.Support or Funding InformationNIH (GM112455 to R.B.), AACR NextGen Grant for Transformative Cancer Research (17‐20‐01‐LYSS) to C.A.L., UMCCC Core Grant (P30 CA046592) to R.B. and C.A.L.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.