Nitric oxide : biology and chemistry最新文献

{"title":"Nitric oxide tuning enhances cytotoxicity and reduces inflammation in prostate cancer nanotherapy.","authors":"Joana Claudio Pieretti, Giovana Marchini Armentano, Marcela Sorelli Carneiro-Ramos, Amedea Barozzi Seabra","doi":"10.1016/j.niox.2025.08.001","DOIUrl":"10.1016/j.niox.2025.08.001","url":null,"abstract":"<p><p>Modulating intracellular nitric oxide (NO) levels offers a promising strategy to enhance tumor cell sensitivity to nanoparticle-based therapies. In this study, we investigated the impact of intracellular NO modulation in prostate cancer cells (PC3) using S-nitrosoglutathione (GSNO, a NO donor) and L-nitro arginine methyl ester (l-NAME, a nitric oxide synthase (NOS) inhibitor), in combination with cisplatin-loaded zinc oxide nanoparticles (ZnO/CisPt NPs). These nanoparticles, previously shown to exert selective cytotoxicity against PC3 cells, had their therapeutic performance further enhanced by NO modulation, which led to reduced NOS expression and regulation of inflammatory cytokines. Interestingly, both the increase and the depletion of intracellular S-NO levels contributed to tumor cell sensitization to the nanoparticle-based treatment. These results indicate that altering NO balance, regardless of direction, plays a key role in how cells respond to therapy. Our results reinforce the relevance of NO signaling in augmenting the efficacy of nanomedicine approaches while minimizing tumor-associated inflammation, offering a safer and more targeted strategy for prostate cancer treatment with potential for broader applications in oncology.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":"124-131"},"PeriodicalIF":3.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The impact of ciliary length on the mechanical response of osteocytes to fluid shear stress” [Nitric Oxide 155 2025 1–11]","authors":"Dong Ding ,&nbsp;Ran Tian ,&nbsp;Xiao Yang ,&nbsp;Zhe Ren ,&nbsp;Zhi-Cheng Jing ,&nbsp;Xin-Tong Wu ,&nbsp;Lian-Wen Sun","doi":"10.1016/j.niox.2025.09.001","DOIUrl":"10.1016/j.niox.2025.09.001","url":null,"abstract":"","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 38-39"},"PeriodicalIF":3.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of hydrogen sulfide in catalyzing the formation of NO-ferroheme","authors":"Laxman Poudel ,&nbsp;Thilini Karunarathna ,&nbsp;Stephen Baker ,&nbsp;Elmira Alipour ,&nbsp;Matthew R. Dent ,&nbsp;Jesús Tejero ,&nbsp;Mark T. Gladwin ,&nbsp;Anthony W. DeMartino ,&nbsp;Daniel B. Kim-Shapiro","doi":"10.1016/j.niox.2025.09.002","DOIUrl":"10.1016/j.niox.2025.09.002","url":null,"abstract":"<div><div>We recently demonstrated a rapid reaction between labile ferric heme and nitric oxide (NO) in the presence of reduced glutathione (GSH) or other small thiols in a process called thiol-catalyzed reductive nitrosylation, yielding a novel signaling molecule, labile nitrosyl ferrous heme (NO-ferroheme), which we and others have shown can regulate vasodilation and platelet homeostasis. Red blood cells (RBCs) contain high concentrations of GSH, and NO can be generated in the RBC via nitrite reduction and/or RBC endothelial nitric oxide synthase (eNOS) so that NO-ferroheme could, in principle, be formed in the RBC. NO-ferroheme may also form in other cells and compartments, including in plasma, where another small and reactive thiol species, hydrogen sulfide (H₂S/HS⁻), is also present and may catalyze NO-ferroheme formation akin to GSH. Here, we compare the reactivity of GSH and hydrogen sulfide with hemin in physiologically relevant media, including human serum albumin (HSA) and RBC membranes. Strikingly, hydrogen sulfide demonstrated a second-order rate constant over 10 times higher than GSH. We propose that the increased solubility of H₂S vs GSH in lipophilic environments – where labile heme is most readily found – and the increased steric hindrance of the bulkier GSH account for the faster reaction kinetics observed with hydrogen sulfide. Our findings suggest that the hydrogen sulfide-catalyzed reductive nitrosylation reaction produces thionitrous acid (HSNO), which readily undergoes further reactions with excess hydrogen sulfide to form nitrosopersulfide (SSNO⁻) and polysulfides. These results suggest a common theme in thiol-catalyzed reductive nitrosylation of labile ferric heme that could play an important role in NO signaling.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 40-50"},"PeriodicalIF":3.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution and activation of nitrergic neurons in response to aversive stimulus exposure in the Tropidurus hispidus lizard: Involvement of glutamatergic circuitry","authors":"Katty Anne Amador de Lucena Medeiros ,&nbsp;Auderlan Mendonça de Gois ,&nbsp;Rodolfo Silva dos Santos ,&nbsp;Milena Caroline Nunes Monteiro ,&nbsp;Heitor Franco Santos ,&nbsp;Marina Freire de Souza ,&nbsp;Thassya Fernanda Oliveira dos Santos ,&nbsp;Marco Aurelio M. Freire ,&nbsp;Mariza Bortolanza ,&nbsp;Elaine Del-Bel ,&nbsp;José Ronaldo Santos ,&nbsp;Murilo Marchioro","doi":"10.1016/j.niox.2025.08.005","DOIUrl":"10.1016/j.niox.2025.08.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Fear is a response to real aversive stimuli. Studies on phylogenetically distant species like reptiles can offer valuable insights into the neural mechanisms of fear.</div></div><div><h3>Objective</h3><div>To investigate the activation and distribution of nitrergic neurons in the telencephalon of <em>Tropidurus hispidus</em> lizards and evaluate the role of glutamatergic modulation via NMDA receptors following exposure to an aversive stimulus.</div></div><div><h3>Methods</h3><div>Lizards were exposed to a live cat, and 24 h later, NADPH-diaphorase histochemistry was performed in the telencephalon to quantify neuron number and optical density. In the second stage, animals received i.c.v. injections of the NMDA receptor antagonist AP5 (1.25, 2.5, or 5.0 μg/μl), followed by cat exposure and histochemical analysis.</div></div><div><h3>Results</h3><div>Exposure to the cat led to increased freezing time in lizards. These animals also showed an increased number of nitrergic neurons in the dorsal cortex, anterior dorsal ventricular ridge (ADVR), and dorsolateral amygdala, as well as elevated integrated optical density (IOD) in the striatum, ADVR, dorsolateral amygdala and lateral amygdaloid nucleus. The AP5 1.25 and 5.0 μg/μl groups exhibited some head or limb movements even in the presence of the cat. The 1.25 μg/μl group showed reduced neuron counts and IOD in the dorsolateral amygdala; the 2.5 μg/μl and 5.0 μg/μl groups showed reduced IOD and neuron counts in the striatum.</div></div><div><h3>Conclusion</h3><div><em>Tropidurus hispidus</em> lizards show fear-like behavior and decreased exploration after aversive stimuli, with nitric oxide in the telencephalon – particularly in the striatum and dorsolateral amygdala – modulating this response via NMDA receptor activation.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 23-37"},"PeriodicalIF":3.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent roles of endothelial and red blood cell nitric oxide synthase in regulating cardiovascular function during anemia","authors":"Vithya Yogathasan ,&nbsp;Patricia Wischmann ,&nbsp;Isabella Solga ,&nbsp;Lilly Jäger ,&nbsp;Stefanie Becher ,&nbsp;Miriam M. Cortese-Krott ,&nbsp;Norbert Gerdes ,&nbsp;Malte Kelm ,&nbsp;Christian Jung ,&nbsp;Ramesh Chennupati","doi":"10.1016/j.niox.2025.08.004","DOIUrl":"10.1016/j.niox.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Red blood cells (RBCs) express functional endothelial nitric oxide synthase (eNOS), which regulates blood pressure (BP) independently of eNOS in endothelial cells (ECs) and provides cardioprotection during acute myocardial infarction (AMI). The functional role of RBC- and EC- eNOS in anemia remains unknown. This study evaluated the effects of RBC- or EC-specific eNOS deletion on hemodynamics and cardiac function in blood loss anemia.</div></div><div><h3>Methods</h3><div>and resultsAnemia was induced in EC- or RBC-specific eNOS knockout (KO) mice and their respective controls. In vivo flow-mediated dilation (FMD) was preserved in RBC-eNOS-KO mice under both baseline and anemic conditions but was impaired in EC-eNOS-KO mice compared to their respective controls. Wire myograph analysis of aortic rings showed preserved endothelium-dependent relaxation (EDR) in anemic RBC-eNOS-KO mice, while EDR was abolished in anemic EC-eNOS-KO mice relative to controls. Miller catheter BP measurements revealed elevated systolic and diastolic BP in EC-eNOS-KO mice under both baseline and anemic conditions. Both systolic and diastolic BP were increased in RBC-eNOS-KO mice compared to controls, whereas these parameters remained unchanged in anemic RBC-eNOS-KO mice compared to their respective controls. Echocardiography demonstrated preserved cardiac function across all genotypes at baseline, 3 days post-anemia, and 24 h post-reperfused AMI. However, infarct size was significantly increased in anemic RBC-eNOS-KO mice compared to controls.</div></div><div><h3>Conclusions</h3><div>Anemia mitigates the BP elevation caused by RBC-eNOS deletion, while hypertension persists in the absence of endothelial eNOS, highlighting vascular eNOS as the predominant regulator of BP under anemic conditions. RBC-eNOS limits infarct size under anemic conditions.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential role of brain nitric oxide in inhibiting α7 nicotinic acetylcholine receptor-mediated suppression of the micturition reflex in rats","authors":"Nobutaka Shimizu ,&nbsp;Takahiro Shimizu ,&nbsp;Mio Togo ,&nbsp;Youichirou Higashi ,&nbsp;Satoshi Fukata ,&nbsp;Keiji Inoue ,&nbsp;Motoaki Saito","doi":"10.1016/j.niox.2025.07.003","DOIUrl":"10.1016/j.niox.2025.07.003","url":null,"abstract":"<div><div>Brain nitric oxide (NO), produced by NO synthase (NOS), exerts both facilitatory and inhibitory effects on micturition. A functional relationship between NO and nicotinic acetylcholine receptors (nAChRs) has been indicated, and we previously reported that stimulation of brain α7 nAChR suppresses the micturition reflex in rats. In this study, we investigated which brain NOS isozyme is involved in micturition regulation and how NO influences α7 nAChR-mediated suppression. Cystometry was performed in urethane-anesthetized male rats using a bladder catheter. SNAP (NO donor), <span>l</span>-NAME (NOS inhibitor), 3-bromo-7-nitroindazole (neuronal NOS inhibitor), or BYK191023 (inducible NOS inhibitor) was administered intracerebroventricularly (icv) 3 h after the surgery. In some rats, the effects of pre-treated SNAP or <span>l</span>-NAME on PHA568487 (α7 nAChR agonist, icv)-induced responses were assessed. Intercontraction intervals (ICI)—the interval between two voiding bladder contractions—were recorded starting 1 h before the first icv administration. SNAP (30 nmol/rat) shortened ICI, whereas <span>l</span>-NAME (100 nmol/rat) and 3-bromo-7-nitroindazole (100 nmol/rat) prolonged ICI; BYK191023 had no effect. PHA568487 (1 nmol/rat) induced ICI prolongation, but this response was suppressed by SNAP (10 nmol/rat). At a lower dose (0.3 nmol/rat), PHA568487 had no effect on ICI unless <span>l</span>-NAME (30 nmol/rat) was pre-administered, which then revealed its significant ICI-prolonging effect. These findings suggest a possibility that brain endogenous NO, particularly from neuronal NOS, may be involved in the inhibition of brain α7 nAChR-mediated suppression of the micturition reflex in rats.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 116-123"},"PeriodicalIF":3.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric oxide as a biomarker for patients with endometriosis: a systematic review and meta-analysis","authors":"Kelly Campara ,&nbsp;Patrícia Rodrigues ,&nbsp;Fernanda Tibolla Viero,&nbsp;Brenda da Silva,&nbsp;Gabriela Trevisan","doi":"10.1016/j.niox.2025.07.002","DOIUrl":"10.1016/j.niox.2025.07.002","url":null,"abstract":"<div><h3>Background</h3><div>Endometriosis causes pelvic pain, inflammation, and increased oxidative stress levels. To assist in the diagnosis of endometriosis and molecular mechanisms, we propose synthesize the studies that NO levels in different samples using a systematic review and metanalysis. We also evaluate NO levels in different stages of endometriosis.</div></div><div><h3>Material/methods</h3><div>The protocol was registered with PROSPERO (CRD42023397591). We searched for all articles published up to November 2023 that evaluated NO levels in patients with endometriosis compared to control patients. We used the Newcastle-Ottawa Scale (NOS) to estimate the quality of the articles and the risk of bias. Publication bias was assessed using the Egger test and Begg test.</div></div><div><h3>Results</h3><div>In this study, 5795 articles were found, after revision 14 studies with 666 control patients and 881 patients with endometriosis were included. NO levels in the combined analysis of all samples from endometriosis patients were increased compared to control patients. Patients with type III/IV endometriosis showed higher levels of NO compared to controls in peritoneal fluid and serum/plasma. The increase in NO levels in patients with type III/IV endometriosis has a high quality of evidence without publication bias.</div></div><div><h3>Conclusion</h3><div>Here we demonstrate the increase of NO in peritoneal fluid samples from endometriosis patients. Therefore, NO levels may be directly linked to the pathophysiology of endometriosis and can be involved in the severity of endometriosis and inflammatory mechanisms.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 106-115"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Catestatin alleviates PASMC phenotypic switching-mediated pulmonary arterial remodeling in a rat model of MCT-induced pulmonary arterial hypertension by promoting endothelium-derived no synthesis","authors":"Zheyu Liu ,&nbsp;Bo Cui ,&nbsp;Hao Ju ,&nbsp;Tuantuan Tan ,&nbsp;Jinchun Wu ,&nbsp;Manqi Yang ,&nbsp;Saeed Kashkooli ,&nbsp;Mian Cheng ,&nbsp;Gang Wu ,&nbsp;Tao Liu","doi":"10.1016/j.niox.2025.07.001","DOIUrl":"10.1016/j.niox.2025.07.001","url":null,"abstract":"<div><h3>Background</h3><div>Enhancing the nitric oxide (NO) signaling pathway is an effective strategy for treating pulmonary arterial hypertension (PAH). Previous research has found that Catestatin (CST) exerts a negative inotropic effect by upregulating NO production. However, the effect of CST on PAH remains unclear.</div></div><div><h3>Methods</h3><div>In vivo, PAH was induced in rats by monocrotaline (MCT) injection. After MCT administration, continuous CST treatment was applied to the experimental group. At study conclusion, echocardiographic, hemodynamic, and histological assessments were performed. In vitro, the effects of CST on rat pulmonary arterial endothelial dysfunction and phenotypic switching of rat pulmonary arterial smooth muscle cells (rPASMC) under PAH-like conditions were investigated. The role of NO in rPASMC phenotypic switching was also explored.</div></div><div><h3>Results</h3><div>In vivo experiments demonstrated that CST significantly improved right heart structure and function in rats with PAH, reduced pulmonary arterial pressure, and alleviated remodeling of the right ventricle and pulmonary arteries. These effects were likely mediated by upregulation of the eNOS/cGMP/PKG pathway. In vitro, CST promoted endothelial NO synthesis via the PI3K/Akt/eNOS pathway, but had no significant impact on the proliferation or migration of rPASMCs. In contrast, exogenous NO effectively inhibited rPASMC phenotypic switching by arresting the cell cycle at the G0/G1 phase.</div></div><div><h3>Conclusion</h3><div>CST enhances endothelial NO synthesis through the PI3K/Akt/eNOS pathway, which subsequently acts on rPASMCs to inhibit their phenotypic switching via the NO/cGMP/PKG signaling pathway, thereby alleviating pulmonary arterial remodeling in PAH.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 93-105"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inorganic nitrate stores, astrocyte metabolism and brain health: An emerging paradigm","authors":"Mario Siervo ,&nbsp;Giuseppe Verdile ,&nbsp;Barbora Piknova","doi":"10.1016/j.niox.2025.06.005","DOIUrl":"10.1016/j.niox.2025.06.005","url":null,"abstract":"<div><div>Inorganic nitrate plays a crucial role in the regulation of cerebral blood flow and neurotransmission through its conversion to nitric oxide (NO). Astrocytes are star-shaped glial cells and contribute to maintain the blood-brain barrier integrity, regulate neuronal metabolism, support synaptic plasticity and facilitate neurovascular coupling. Inorganic nitrate widely distributed through all organs, with main reservoirs in skeletomuscular and skin tissues. These reserves are easily accessible via bloodstream and processed into nitrite and NO mainly in liver. Processing nitrate/nitrite into NO at organ with main glycogen stores, could suggest an evolutionary coordination between energy metabolism and NO generating pathways. Such spatial arrangement may facilitate the synchronised mobilisation during periods of enhanced metabolic demand, optimising both fuel utilisation and vascular response and assuring optimal fuel distribution. Astrocytes store glycogen in the brain, which support neuronal metabolism during periods of increased neural activity and hypoglycaemia.</div><div>This review explores the hypothesis that inorganic nitrate may be stored alongside glycogen in astrocytes and serve as critical reserves for NO production in the brain, particularly during hypoxic conditions. We examine the emerging evidence that astrocytes serve as key mediators in this alternative nitrate-nitrite-NO pathway, potentially influencing cerebrovascular regulation, neuronal energetics, and cognitive function. The integration of findings across molecular, cellular, and systems neuroscience offers new perspectives on how inorganic nitrate intake might support brain metabolism and could inform both preventive strategies and therapeutic interventions for neuro-degenerative disorders such as age-related dementia, stroke or Parkinson's Disease.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 76-81"},"PeriodicalIF":3.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-mercaptopyruvate sulfurtransferase resides on the inner mitochondrial membrane","authors":"Antonia Katsouda ,&nbsp;Eleni Vasilaki ,&nbsp;Markos Fountoulakis ,&nbsp;Ioanna Tremi ,&nbsp;Sophia Havaki ,&nbsp;Vassilios Myrianthopoulos ,&nbsp;Vassilis G. Gorgoulis ,&nbsp;Emmanuel Mikros ,&nbsp;Andreas Papapetropoulos","doi":"10.1016/j.niox.2025.06.004","DOIUrl":"10.1016/j.niox.2025.06.004","url":null,"abstract":"<div><div>3-mercaptopyruvate sulfurtransferase (MPST) is an enzyme implicated in the generation of the gasotransmitter hydrogen sulfide (H₂S). Unlike, the other two H₂S-synthesizing enzymes cystathionine gamma lyase (CSE) and cystathionine beta synthase (CBS), MPST is found in the mitochondria. However, the mechanisms through which MPST gains access to the mitochondria and its exact localization within this organelle remain unclear. Using immunogold electron microscopy staining, we localized MPST on the inner mitochondrial membrane. To study the pathway of mitochondrial entry for MPST, pharmacological inhibitors of different components of the translocase of outer/inner membrane were used. In line with the observation that ΜPST is found on the inner mitochondrial membrane, inhibition of TIM23 blocked MPST mitochondrial entry. Generation of N-terminally truncated forms of ΜPST did not interfere with the ability of the enzyme to gain access into the mitochondria, suggesting that an N-terminal pre-sequence does not mediate MPST mitochondrial entry. In agreement to this finding, cytosolic and mitochondrial MPST had a similar molecular weight. Interestingly, N-terminally deleted MPST exhibited reduced expression levels, indicating that this part of the enzyme is required for protein stability. Molecular dynamics simulations confirmed that deletion of the first 39 amino acids of the enzyme destabilizes the protein. Our findings reveal that MPST is present on the inner mitochondrial membrane and that its entry into mitochondria does not involve the N-terminus of the protein.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 67-75"},"PeriodicalIF":3.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}