Sulfide-sensitive cellular targets

Sulfide-sensitive cellular targets represent a diverse collective of proteins, enzymes, and ion channels whose biological activities are modulated by hydrogen sulfide (H2S), a critical endogenous gasotransmitter [1, 3]. These targets include mitochondrial cytochrome c oxidase (Complex IV), which is inhibited by H2S at high concentrations, leading to the cessation of cellular respiration and potential toxicity [2, 5]. Conversely, at physiological levels, H2S activates ATP-sensitive potassium (KATP) channels to induce vasodilation and regulates various enzymes, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), through a post-translational modification known as S-sulfhydration or persulfidation [7, 9]. This modification also affects the p65 subunit of NF-kB, promoting anti-inflammatory and anti-apoptotic signaling pathways [3, 5]. Dysregulation of these sulfide-sensitive pathways is implicated in a wide range of pathologies, including cardiovascular diseases, neurodegeneration, diabetes, and chronic inflammation [10, 11]. Pharmacological strategies targeting these molecules involve the use of H2S donors like GYY4137 and SG-1002 to enhance protective signaling, or inhibitors of H2S-producing enzymes like cystathionine gamma-lyase (CSE) to mitigate excessive production [3, 7]. However, the therapeutic application is challenged by a narrow window between beneficial signaling and mitochondrial toxicity, as well as the systemic nature of H2S effects [1, 10].

Other names

H2S-sensitive proteinsHydrogen sulfide molecular targetsPersulfidation targetsS-sulfhydration targets

Modulation of protein function via S-sulfhydration (persulfidation) of cysteine residues, binding to metal centers such as heme iron in cytochrome c oxidase, and direct scavenging of reactive oxygen species (ROS).