Cell calcium最新文献

{"title":"Activation of TRPM8 promotes K+ secretion in rat epididymal epithelium","authors":"Zi-Yang Huang ,&nbsp;Yu-Yun Zhou ,&nbsp;Xin-Ni Sun ,&nbsp;Yi-Ran Ye ,&nbsp;Fei-Fei Huang ,&nbsp;Jie Sheng ,&nbsp;Dan-Yang Zou ,&nbsp;Ting-Ting Tang ,&nbsp;Zi-Ying Yang ,&nbsp;Tong-Zhen Weng ,&nbsp;Xin-Rui Ling-Hu ,&nbsp;Wai Hou Tang ,&nbsp;Yun-Xin Zhu ,&nbsp;Lei Chen ,&nbsp;Su Qu ,&nbsp;Wen-Liang Zhou ,&nbsp;Yi-Lin Zhang","doi":"10.1016/j.ceca.2026.103117","DOIUrl":"10.1016/j.ceca.2026.103117","url":null,"abstract":"<div><div>The epididymis establishes a unique hyper-potassium luminal microenvironment essential for sperm maturation and storage, which is largely orchestrated by epididymal epithelial ion transport. Although the transient receptor potential melastatin 8 (TRPM8) is broadly expressed across various organ systems, its physiological role in male reproduction has remained largely unexplored. This study demonstrated that TRPM8 was predominantly expressed in rat epididymal epithelial cells. Activation of TRPM8 by either the exogenous agonist WS-12 or the endogenous hormone testosterone triggered a decrease in short-circuit current (<em>I</em>_SC) response in primary cultured rat epididymal epithelial cells. This <em>I</em>_SC response was suppressed by removal of extracellular K⁺ or by pharmacological inhibition of Ca²⁺-activated potassium channels (K_Ca), Na⁺-K⁺ ATPase or the Na⁺-K⁺-Cl⁻ cotransporter, indicating that TRPM8 mediated transepithelial K⁺ secretion in a Ca²⁺-dependent manner. Consistently, TRPM8 activation increased intracellular Ca²⁺ concentration in primary rat epididymal epithelial cells, which could be abolished by the removal of extracellular Ca²⁺. An <em>in vivo</em> study showed functional TRPM8 deficiency disrupted the luminal hyper-potassium microenvironment in rat epididymis. Moreover, impaired sperm motility and reduced male fertility were observed in TRPM8-deficient rats, which could be rescued by restoring luminal hyper-potassium microenvironment through K_Ca activation. Overall, this study elucidates a crucial role for TRPM8 in establishing the epididymal hyper-potassium microenvironment, offering valuable insights into the physiological function of TRPM8 in male reproductive health and disease.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"134 ","pages":"Article 103117"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957837","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":"A NOX2-independent mechanism of Hv1 channel activation promotes inflammatory cytokine release from BV-2 microglia via intracellular Ca2+ mobilisation","authors":"Ashutosh Sharma ,&nbsp;Priyanka Yadav ,&nbsp;Shivani Yadav ,&nbsp;Vikash Kumar ,&nbsp;Kunvar Ravendra singh ,&nbsp;Madhavi Ranawat ,&nbsp;Shivani Pal ,&nbsp;Ankita Yadav ,&nbsp;Gokul Krishnan Nagendran ,&nbsp;Sunil P. Kase ,&nbsp;Yaduvender Yadav ,&nbsp;Satish K. Mudedla ,&nbsp;Valmik S. Shinde ,&nbsp;Aravind Singh Kshatri","doi":"10.1016/j.ceca.2026.103122","DOIUrl":"10.1016/j.ceca.2026.103122","url":null,"abstract":"<div><div>Microglia are the primary immune cells to sense and respond to all the pathological events in the brain. Voltage-gated proton channels (Hv₁) are specifically expressed in the microglia to regulate their intracellular pH and contribute to redox homeostasis. Our previous work identified that S-023–0515 is a novel activator of microglial Hv₁ channels, inducing neuroinflammation through unknown mechanisms. In this study, we demonstrate the direct binding of S-023–0515 onto the Hv₁ channel using molecular docking, molecular dynamics (MD) simulations, and Bio-layer interferometry (BLI) techniques. Treatment with S-023–0515 induced a sustained intracellular alkalization, resulting in a gradual increase in cytosolic Ca²⁺ levels. None of the major plasma membrane Ca²⁺ ion channels, such as TRPV1, Cav1.2, ASIC and P2X7, nor intracellular Ca²⁺ release channels were found to be involved in S-023–0515-induced Ca²⁺ increase. This mobilisation of Ca²⁺ occurred through the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), as its inhibition annulled the S-023–0515-mediated Ca²⁺ rise. Hv₁-mediated Ca²⁺ signaling further promoted NF-κB activation leading to a steady increase in proinflammatory cytokines, such as TNF-α and IL-1β, in BV-2 microglial cells, representing an inflammatory microglial phenotype. Notably, the proinflammatory response was solely attributable to Hv₁ channel activation because neither NOX2 stimulation nor local cellular pH was altered following S-023–0515 treatment. Together, these findings suggest that NOX2-independent activation of Hv₁ channels triggers a Hv₁-SERCA-Ca²⁺-NF-κΒ signalling cascade, disrupting intracellular Ca²⁺ homeostasis and leading to microglial neurotoxicity.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"134 ","pages":"Article 103122"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046153","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":"Reticulocalbin1-mediated regulation of calcium homeostasis in naïve T lymphoncytes","authors":"Takeru Kobayashi ,&nbsp;Wooseok Seo ,&nbsp;Norihisa Ichimura ,&nbsp;Yusuke Urata ,&nbsp;Hideharu Hibi ,&nbsp;Hiroyoshi Nishikawa","doi":"10.1016/j.ceca.2026.103121","DOIUrl":"10.1016/j.ceca.2026.103121","url":null,"abstract":"<div><div>Reticulocalbin1 (RCN1), a calcium-binding protein localized in the endoplasmic reticulum (ER), is implicated in cancer progression, but its role in the immune system remains poorly understood. To clarify the function of RCN1, we generated a RCN1-deficient (<em>Rcn1^−/−</em>) mice using CRISPR-Cas9 system. Immunological characterization by flow cytometry revealed that while T cell populations in the spleen were unaffected, the proportion of CD8 single-positive (SP) thymocytes was significantly reduced in <em>Rcn1^−/−</em> mice. In contrast, <em>in vitro</em> stimulation of splenic CD8⁺ T cells revealed no significant differences in the expression of cell surface activation markers or cytokines between <em>Rcn1^+/+</em> and <em>Rcn1^−/−</em> mice. Functional analysis showed that at baseline, cytosolic calcium levels were significantly higher in <em>Rcn1^+/+</em> CD8⁺ T cells. In contrast, stimulus-induced calcium responses, including ER calcium release, extracellular calcium entry, and TCR-dependent calcium flux, were preserved in both genotypes. Collectively, our results suggest that RCN1 contributes to the fine-tuning of ER-associated calcium handling in naïve (non-activated) T cells, thereby modulating basal cytosolic calcium levels and supporting efficient thymic CD8⁺ T cell development.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"134 ","pages":"Article 103121"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036035","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":"BDNF prevents amyloid-β-induced exacerbation of mGluR5-driven Ca2+ transients in astrocytes through TrkB-Tc activation","authors":"Pedro Avelar ,&nbsp;Tatiana P. Morais ,&nbsp;Haissa de Castro-Abrantes ,&nbsp;Adam Armada-Moreira ,&nbsp;Joana Gonçalves-Ribeiro ,&nbsp;Cláudia A. Valente ,&nbsp;Ana Maria Sebastião ,&nbsp;Maria José Diógenes ,&nbsp;Sandra H. Vaz","doi":"10.1016/j.ceca.2026.103119","DOIUrl":"10.1016/j.ceca.2026.103119","url":null,"abstract":"<div><div>Brain-derived neurotrophic factor (BDNF) is a neurotrophin that, through the activation of its full length receptor, TrkB-FL, plays a pivotal role in neuroprotection, namely against neuronal toxicity mediated by amyloid-β peptide (Aβ). In astrocytes, the increase of calcium (Ca²⁺) signaling due the increase of metabotropic glutamate receptor type 5 (mGluR5) levels, induced by Aβ, has been considered deleterious for astrocytic function. In adition BDNF also increases intracellular calcium concentration ([Ca²⁺]ᵢ), in astrocytes, via activation of the truncated TrkB receptor isoform, TrkB-Tc. While the role of BDNF, in neurons, is well established, in terms of neuroprotection, its role in astrocytes, particularly in Aβ-induced toxicity conditions, remains less clear. Thus, this study aimed to evaluate the interplay between BDNF and Aβ in the modulation of [Ca²⁺]_i signaling in primary cultures of cortical astrocytes.</div><div>Ca²⁺ transients were induced by the activation of mGluR5 through the application of its agonist DHPG. In astrocytes pre-exposed to Aβ_25–35 (10 µM, for 48–72 h), the Ca²⁺ transient amplitude was significantly increased compared to the control. A similar increase was observed in astrocytes incubated for 48 h with BDNF (20 ng/mL), or when astrocytes were simultaneously exposed to BDNF and Aβ. The effect of BDNF was mediated by TrkB-Tc since it was prevented by a cocktail of the three siRNAs against TrkB-Tc expression. mGluR5 levels were significantly increased in astrocytes pre-exposed to Aβ, while exposure to BDNF did not affect mGluR5 levels. Importantly, while the presence of Aβ did affect TrkB-Tc receptor levels in astrocytes, the presence of BDNF prevented the increase in mGluR5 levels caused by Aβ thus precluding a further exacerbation of Ca²⁺ transients caused by Aβ.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"134 ","pages":"Article 103119"},"PeriodicalIF":4.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035983","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":"ER calcium stores contribute to glucose-induced Ca2+ waves and intercellular connectivity in mouse pancreatic islets","authors":"Luis Fernando Delgadillo-Silva ,&nbsp;Karen Dakessian ,&nbsp;Audrey Provencher-Girard ,&nbsp;William E. Louch ,&nbsp;Guy A. Rutter","doi":"10.1016/j.ceca.2025.103093","DOIUrl":"10.1016/j.ceca.2025.103093","url":null,"abstract":"<div><div>Defective insulin secretion is a hallmark of diabetes mellitus. Glucose-induced Ca²⁺ oscillations are critical for the stimulation of insulin secretion, though the mechanisms through which these propagate across the islet are poorly understood. Here, we use beta cell-targeted GCaMP6f to explore the role of endoplasmic reticulum (ER) Ca²⁺ mobilization in response to submaximal (11 mM) or hyperglycemic (25 mM) glucose, mimicking diabetes. Inhibition of inositol 1,4,5-trisphosphate (IP₃) receptors, and other ion channels, with 2-aminoethoxydiphenyl borate (2-APB), had minimal effects on the initial peak or intercellular connectivity provoked by 11 mM glucose. However, 2-APB lowered subsequent glucose-induced cytosolic Ca²⁺increases and connectivity at both 11 and 25 mM glucose. Unexpectedly, the activation of IP₃ receptors with the muscarinic acetylcholine receptor agonist carbachol had minimal impact on the initial peak elicited by 11 mM glucose, but Ca²⁺ waves at 11 and 25 mM glucose were more poorly coordinated. To determine whether ER calcium mobilization was sufficient to initiate Ca²⁺ waves we next blocked sarco(endo)plasmic Ca²⁺ ATPase (SERCA) pumps with thapsigargin, whilst preventing plasma membrane depolarization with the K_ATP-channel opener, diazoxide. Under these conditions, an initial cytosolic Ca²⁺increase was followed by secondary Ca²⁺ waves that subsided slowly. The application of carbachol alongside diazoxide still enhanced Ca²⁺dynamics, though activity was uncoordinated. After genetic deletion of SERCA2 in beta cells, Ca²⁺wave frequency, but not connectivity, were lowered. Our results show that ER Ca²⁺ mobilization plays a relatively minor role in the initiation and propagation of Ca²⁺ waves in response to glucose but is needed for sustained Ca²⁺waves.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"133 ","pages":"Article 103093"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787209","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":"GCaMP6f-expressing chromaffin cells in murine adrenal slices exhibit dynamic spontaneous calcium responses that do not require nerve input","authors":"Nicole M. Procacci ,&nbsp;Gale L. Craviso ,&nbsp;Normand Leblanc ,&nbsp;Josette Zaklit ,&nbsp;Jihwan Yoon ,&nbsp;Salah A Baker ,&nbsp;Thomas W. Gould","doi":"10.1016/j.ceca.2025.103104","DOIUrl":"10.1016/j.ceca.2025.103104","url":null,"abstract":"<div><div>Chromaffin cells of the adrenal medulla exhibit spontaneous action potentials and intracellular Ca²⁺ responses that result in catecholamine secretion when dissociated in vitro. However, spontaneous activity in these cells is nearly abolished when splanchnic nerve input is blocked in vivo. To address this discrepancy, we examined spontaneous Ca²⁺ responses in chromaffin cells in an intermediate preparation, adrenal slices from transgenic mice expressing the genetically-encoded Ca²⁺ indicator GCaMP6f selectively in these cells. Within this preparation, the three-dimensional structure and extracellular environment surrounding chromaffin cells is retained, as is input from distal splanchnic nerve terminals, which spontaneously release the neurotransmitter acetylcholine. Chromaffin cells within these slices displayed spontaneous Ca²⁺ responses with frequencies and amplitudes that varied greatly within and between individual cells. However, population averages remained stable, providing a tool to measure the cellular and molecular mechanisms underlying these responses. While overall average frequencies and amplitudes of spontaneous Ca²⁺ responses depended on the influx of extracellular Ca²⁺ through voltage-gated Ca²⁺ channels, they did not require Ca²⁺ release from intracellular stores, splanchnic nerve input or activation of voltage-gated sodium channels. Together, these results suggest that spontaneous activity in chromaffin cells in adrenal slices is generated autonomously, similar to that in dissociated chromaffin cells. By contrast, spontaneous activity in chromaffin cells in intact animals likely represents a distinct form that depends on basal input from intact splanchnic nerve. This study provides a foundation to further explore the diverse mechanisms mediating chromaffin cell activation.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"133 ","pages":"Article 103104"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733566","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":"The handshake between the continuous remodeling of the endoplasmic reticulum and the store-operated calcium entry","authors":"Alicia Sampieri ,&nbsp;Alexander Asanov ,&nbsp;Aaron Pavel Rodríguez-Hernández ,&nbsp;Ileana Tobías-Juárez ,&nbsp;Luis Vaca","doi":"10.1016/j.ceca.2025.103100","DOIUrl":"10.1016/j.ceca.2025.103100","url":null,"abstract":"<div><div>The two main components of store-operated calcium entry (SOCE) are the ion channel Orai1 and the multifunctional protein STIM1. Recently STIM1 has been recognized as a microtubule plus end tracking protein involved in remodeling of the endoplasmic reticulum. However, the relationship between ER remodeling and SOCE are poorly understood. In the present study we have found that activation of Orai1 channels by the expression of the SOAR (STIM1 Orai activating region) from STIM1 induces Orai1 puncta formation and SOCE but does not alter the role of STIM1 in ER remodeling. Furthermore, expression of the STIM1-EB1-D (the STIM1-EB1 association domain) from STIM1 significantly reduces SOCE and prevents the traveling of STIM1 in ER projections. However, ER projections driven by EB1 remained unaffected. These findings suggest that there may be several mechanisms responsible for ER remodeling but only one in which STIM1 participates. This type of ER remodeling mechanism where STIM1 plays an active role participates in the control of SOCE.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"133 ","pages":"Article 103100"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667198","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":"Ca2+/calmodulin-driven functions mediated by extracellular vesicles: a physiopathological perspective","authors":"Juan Alcalde ,&nbsp;Ester Martín-Villar ,&nbsp;Martin W. Berchtold ,&nbsp;Antonio Villalobo","doi":"10.1016/j.ceca.2025.103105","DOIUrl":"10.1016/j.ceca.2025.103105","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), including exosomes and microvesicles, secreted by a wide range of eukaryotic cells, are now well-established mediators of intercellular communication, acting through their uptake by recipient cells at local or distant sites. This occurs after delivering their cargo, a variety of RNAs, lipids, and proteins, which regulate many cellular functions in health and disease states. Among the exosomal cargos, the Ca²⁺-sensor protein calmodulin (CaM), as well as several Ca²⁺/CaM-regulated proteins, are frequently found in EVs, potentially playing important roles in the function of target cells. In addition, RNAs, which control the expression (mRNAs) or downregulation (miRNAs, lncRNAs) of Ca²⁺/CaM-regulated systems, are present in EVs, contributing to Ca²⁺ signaling processes when transferred into target cells. We discuss the involvement of exosomal CaM signaling systems in the pathophysiology of some high-incidence diseases affecting the heart and the nervous system. In this group, the contribution of Ca²⁺/CaM-regulated systems to tumor cells behavior in a wide range of organs is explored in more detail. In addition, some diseases of the kidneys, lungs, liver, the immune system, the eyes and the pancreas are considered. Finally, we highlight selected examples in which isolated exosomes modulating Ca²⁺/CaM pathways have been investigated as potential therapeutic agents.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"133 ","pages":"Article 103105"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780275","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":"Emerging therapeutics targeting the PI3K/Akt/GSK-3β in calcium dysregulation in Alzheimer’s disease","authors":"Simran Soni,&nbsp;Ginpreet Kaur","doi":"10.1016/j.ceca.2025.103107","DOIUrl":"10.1016/j.ceca.2025.103107","url":null,"abstract":"<div><div>Calcium serves as an important cellular messenger in neurons, which needs to be regulated at optimal concentrations intracellularly for normal functioning of nerve cells. The dysregulation of calcium represents a relatively newer target associated with several neurodegenerative disorders such as Alzheimer’s disease. The growing incidence of Alzheimer’s disease, which offers symptomatic treatments for its underlying pathology, has prompted the exploration of novel targets. It has been demonstrated that the PI3K/Akt/GSK-3β pathway is essential for neuroprotection, increasing cell survival by promoting cell division and preventing apoptosis, which are regulated by extracellular calcium. Inhibition of neuroprotective PI3K activation by calcium dyshomeostasis can lead to dephosphorylating Akt. These cause hyperphosphorylation of tau protein through the overactivation of GSK-3β, which leads to the formation of neurofibrillary tangles and deposition of amyloid protein that will exacerbate cognitive decline and Alzheimer’s disease. This comprehensive review will provide the insights of pathogenic mechanisms involved in calcium dysfunction associated with PI3K/Akt/GSK-3β signaling in the progression of the disease to identify novel targets. Also, it emphasizes emerging therapeutics, including modulators, which can be targeted to maintain the calcium level in the brain and ameliorate the pathology of the disease.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"133 ","pages":"Article 103107"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836666","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":"Ablation of mitochondrial calcium uniporter alleviates cardiac dysfunction in type 1 diabetes","authors":"Arpita Deb ,&nbsp;Valeria Gomez ,&nbsp;Yujia Cheng ,&nbsp;Zhuoxin Li ,&nbsp;Jinying Yang ,&nbsp;Imtiaz Dowllah ,&nbsp;Ngoc Nguyen ,&nbsp;Oluwabori Adekanye ,&nbsp;Ashley J. Smuder ,&nbsp;Zhiyong Cheng ,&nbsp;Bin Liu","doi":"10.1016/j.ceca.2025.103106","DOIUrl":"10.1016/j.ceca.2025.103106","url":null,"abstract":"<div><div>Calcium (Ca²⁺) enters the mitochondria primarily through the mitochondria calcium uniporter (MCU). Conflicting results have been reported regarding the role of MCU in metabolic heart disease. Therefore, we employed a cardiomyocyte-specific MCU knockout (KO) model to assess its impact on the development of diabetic cardiomyopathy (DCM). Type 1 diabetes was induced in mice through streptozotocin (STZ) injection. The study included four groups: a wild-type (WT) control, two STZ-injected groups, designated as WT-STZ and MCU^KO-STZ, and a MCU^KO control. WT-STZ mice developed DCM, exhibiting contractile dysfunction (assessed by echocardiography) and ventricular arrhythmias (identified via electrocardiogram). Fluorescent imaging of isolated WT-STZ myocytes revealed impaired Ca²⁺ homeostasis and increased reactive oxygen species (ROS) production. Histological staining of WT-STZ cardiac tissue showed cellular hypertrophy and increased apoptosis. Mitochondrial energetics was also compromised in the WT-STZ model. MCU ablation significantly improved cardiac function in MCU^KO-STZ mice, which maintained normal contractile function. Both cellular and in vivo arrhythmias were ameliorated in MCU^KO-STZ. MCU^KO-STZ myocytes exhibited <em>improved</em> Ca²⁺ handling and lower ROS emission. Hypertrophy and apoptosis were also alleviated in this group. Additionally, mitochondrial energetics, while not reversed, exhibited a slight trend toward improvement. Our study suggests that MCU ablation attenuates DCM progression. Inhibiting MCU-dependent Ca²⁺ entry may serve as a potential therapeutic strategy for type 1 diabetic cardiomyopathy by preventing arrhythmogenesis and pathological remodeling.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"133 ","pages":"Article 103106"},"PeriodicalIF":4.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827055","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}