ETHE1

Last update 08 May 2025

Basic Info

Synonyms

ETHE1, ETHE1 persulfide dioxygenase, Ethylmalonic encephalopathy protein 1

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Introduction

Sulfur dioxygenase that plays an essential role in hydrogen sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide (H(2)S) is first oxidized by SQRDL, giving rise to cysteine persulfide residues. ETHE1 consumes molecular oxygen to catalyze the oxidation of the persulfide, once it has been transferred to a thiophilic acceptor, such as glutathione (R-SSH). Plays an important role in metabolic homeostasis in mitochondria by metabolizing hydrogen sulfide and preventing the accumulation of supraphysiological H(2)S levels that have toxic effects, due to the inhibition of cytochrome c oxidase. First described as a protein that can shuttle between the nucleus and the cytoplasm and suppress p53-induced apoptosis by sequestering the transcription factor RELA/NFKB3 in the cytoplasm and preventing its accumulation in the nucleus (PubMed:12398897).

100 Clinical Results associated with ETHE1

100 Translational Medicine associated with ETHE1

0 Patents (Medical) associated with ETHE1

109

Literatures (Medical) associated with ETHE1

01 Mar 2025·Archives of Toxicology

Mitigation of depleted uranium-induced mitochondrial damage by ethylmalonic encephalopathy 1 protein via modulation of hydrogen sulfide and glutathione pathways

Article

Author: Li, Juan ; Ran, Yonghong ; Tan, Huanhuan ; Shen, Li ; Li, Yong ; Li, Wenrun ; Hao, Yuhui ; Liu, Suiyi ; Zhao, Yazhen

Depleted uranium (DU) is a byproduct of uranium enrichment, which can cause heavy-metal toxicity and radiation toxicity as well as serious damage to the kidneys. However, the mechanism of renal injury induced by DU is still unclear. This study aimed to explore the role of ethylmalonic encephalopathy 1 (ETHE1) in DU-induced mitochondrial dysfunction and elucidate the underlying mechanisms. Using ETHE1 gene knockout C57BL/6 mice (10 mg/kg DU) and renal cell models (500 µM DU) exposed to DU, we observed significantly reduced levels of hydrogen sulfide (H₂S) and glutathione (GSH), alongside decreased adenosine triphosphate (ATP) content and increased oxidative stress. Our results demonstrated that knocking out or silencing ETHE1 led to a significant reduction in H₂S and GSH levels, whereas the opposite occurred when was ETHE1 overexpressed. When the H₂S donor sodium hydrosulfide and GSH precursor N-acetylcysteine were used to treat animals or cells, cellular ATP levels were increased, oxidative stress markers were reduced, and kidney damage was mitigated. In addition, H₂S and GSH interacted with each other after DU poisoning. These findings suggest that the ETHE1/H₂S/GSH pathway plays a critical role in mediating DU-induced mitochondrial dysfunction in renal cells, highlighting potential therapeutic targets for mitigating the harmful effects of DU. Thus, this study expands our understanding of DU-induced renal damage pathways, providing avenues for further research and intervention strategies.

01 Feb 2025·Pharmacology & Therapeutics

Essential role of sulfide oxidation in brain health and neurological disorders

Review

Author: Kanemaru, Eiki ; Ichinose, Fumito

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.

01 Dec 2024·Advanced Healthcare Materials

Viscoelasticity of Hyaluronic Acid Hydrogels Regulates Human Pluripotent Stem Cell‐derived Spinal Cord Organoid Patterning and Vascularization

Article

Author: Zhou, Yi ; Chen, Xingchi ; Zeng, Changchun ; Wang, Xueju ; Li, Yan ; Ali, Jamel ; Driscoll, Tristan ; McDaniel, Garrett ; Liu, Chang ; Zeng, Olivia

AbstractRecently, it has been recognized that natural extracellular matrix (ECM) and tissues are viscoelastic, while only elastic properties have been investigated in the past. How the viscoelastic matrix regulates stem cell patterning is critical for cell‐ECM mechano‐transduction. Here, this study fabricated different methacrylated hyaluronic acid (HA) hydrogels using covalent cross–linking, consisting of two gels with similar elasticity (stiffness) but different viscoelasticity, and two gels with similar viscoelasticity but different elasticity (stiffness). Meanwhile, a second set of dual network hydrogels are fabricated containing both covalent and coordinated cross–links. Human spinal cord organoid (hSCO) patterning in HA hydrogels and co‐culture with isogenic human blood vessel organoids (hBVOs) are investigated. The viscoelastic hydrogels promote regional hSCO patterning compared to the elastic hydrogels. More viscoelastic hydrogels can promote dorsal marker expression, while softer hydrogels result in higher interneuron marker expression. The effects of viscoelastic properties of the hydrogels become more dominant than the stiffness effects in the co‐culture of hSCOs and hBVOs. In addition, more viscoelastic hydrogels can lead to more Yes‐associated protein nuclear translocation, revealing the mechanism of cell‐ECM mechano‐transduction. This research provides insights into viscoelastic behaviors of the hydrogels during human organoid patterning with ECM‐mimicking in vitro microenvironments for applications in regenerative medicine.

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ETHE1

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