Cell calcium最新文献

{"title":"Protein diversity in store-operated calcium entry components and their related variants.","authors":"Mélanie Robitaille","doi":"10.1016/j.ceca.2025.103066","DOIUrl":"10.1016/j.ceca.2025.103066","url":null,"abstract":"<p><p>Protein diversity is a fundamental biological process that enhances the functional complexity of cellular signaling pathways. This diversity arises through multiple molecular mechanisms such as gene duplication, alternative splicing, and alternative translation initiation, which together expand the proteome landscape. Calcium signaling showcases this diversity, with several channels, pumps, and regulatory proteins expressed as multiple isoforms and variants. Within the store-operated calcium entry pathway, protein diversity is evident in the existence of distinct paralogs of ORAI channels and STIM proteins. The additional presence of numerous isoforms and variants of ORAI and STIM shapes the store-operated calcium entry pathway, providing flexibility to cellular calcium regulation in various contexts. Deciphering how protein diversity modulates store-operated calcium entry function is essential for advancing our understanding of calcium signaling in both health and disease.</p>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"131 ","pages":"103066"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811841","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":"TRPV1 signaling in skeletal muscle: A mini review of physiological and pathological roles.","authors":"Xiaoqing Ding, Chenyu Zhu, Qi Lu, Yuhao Zhang, Binghong Gao","doi":"10.1016/j.ceca.2025.103057","DOIUrl":"10.1016/j.ceca.2025.103057","url":null,"abstract":"<p><p>Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel that is mainly sensitive to stimuli such as high temperature, acidic environment, and capsaicin. Studies have reported that TRPV1 is expressed in skeletal muscle tissues and is involved in the regulation of a variety of physiological and pathological processes in skeletal muscle, but its regulatory mechanisms have not been analyzed and discussed. For this reason, we summarized the role of TRPV1 in skeletal muscle function and the mechanism of its influence on skeletal muscle-related physiopathological changes, such as myotube formation, inflammation, autophagy, mitochondrial biogenesis, and energy metabolism, which provides a theoretical basis and therapeutic target for understanding TRPV1 regulation of skeletal muscle-related diseases.</p>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"131 ","pages":"103057"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811842","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":"Pathological calcium influx through amyloid beta pores disrupts synaptic function","authors":"Temitope Adeoye,&nbsp;Ghanim Ullah","doi":"10.1016/j.ceca.2025.103083","DOIUrl":"10.1016/j.ceca.2025.103083","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is characterized by profound disruption of synaptic function, with mounting evidence suggesting that amyloid-β (Aβ) oligomers disrupt calcium (Ca²⁺) homeostasis through membrane pore formation. While these pores are known to alter intracellular Ca²⁺ dynamics, their immediate impact on synaptic transmission and potential interaction with Familial AD (FAD)-associated endoplasmic reticulum (ER) dysfunction remains unclear. Here, we extend our previously developed model of presynaptic Ca²⁺ dynamics to examine how Aβ pores alter exocytosis and how such disruptions may manifest in the presence of FAD-associated ER dysfunction. Our model reveals that Aβ pores fundamentally alter both the timing and strength of neurotransmitter release. Unexpectedly, the impact of pores on synaptic function depends critically on their pattern of activity, where continuous pore activity leads to synaptic hyperactivation, while brief periods of intense pore activity trigger lasting hypoactivation at short timescales. These effects manifest most strongly in synapses with low and intermediate release probabilities, highlighting the established selective vulnerability of such synaptic configurations. We find that Aβ pores and FAD-driven ER Ca²⁺ dysregulation form an integrated pathological unit through bidirectional coupling of their respective Ca²⁺ microdomains to create complex patterns of disruptions. This coupling creates a feedback loop that produces an additive effect on neurotransmitter release during brief stimulations, but non-additive effects during sustained activity that promotes a shift towards asynchronous release. Surprisingly, our simulations predict that extended pore activity does not worsen indefinitely but only produces a modest additional disruption beyond initial pore formation that is likely determined by the intrinsic properties of the synapse. These findings indicate that early synaptic dysfunction in AD may arise from subtle perturbations in the temporal coordination of release rather than gross Ca²⁺ dysregulation, providing new mechanistic insights into the progressive nature of Aβ-driven synaptic failure in AD.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103083"},"PeriodicalIF":4.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217036","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":"Neuronal regulation of myenteric interstitial cells of Cajal (ICC-MY) in the proximal colon","authors":"Salah A. Baker ,&nbsp;Bernard T. Drumm ,&nbsp;Manushri Karwa ,&nbsp;Katy M. Thompson ,&nbsp;Benjamin Smith ,&nbsp;Kenton M. Sanders","doi":"10.1016/j.ceca.2025.103082","DOIUrl":"10.1016/j.ceca.2025.103082","url":null,"abstract":"<div><div>Interstitial cells of Cajal (ICC) generate contractile patterns of colonic motility. We investigated innervation of ICC within the plane of the myenteric plexus (ICC-MY) in proximal colon using mice expressing GCaMP6f in ICC. ICC-MY generated localized Ca²⁺ transients that couple to activation of ANO1 channels, a Ca²⁺-activated Cl^- conductance. ICC are electrically coupled to SMCs, so activation or suppression of currents in ICC affects excitability of SMCs. ICC-MY displayed tonic inhibition, as the neurotoxin, TTX, increased the frequency of Ca²⁺ transients. Tonic inhibition was mimicked by a nitric oxide donor, NONOate, and by a guanylate cyclase agonist (Bay 58–2667). In contrast ODQ mimicked effects of TTX, increasing Ca²⁺ transients. Carbachol (CCh) increased Ca²⁺ transients in ICC-MY, and these effects were mediated by M3 muscarinic receptors. Neostigmine, also increased Ca²⁺ transients, suggesting there is tonic activation of enteric excitatory neurons in colonic muscles. Substance P and antagonists of NK1 and NK2 receptors had no effect on Ca²⁺ transients in ICC-MY. Electrical field stimulation (EFS), under conditions that emphasized excitatory neural responses, enhanced Ca²⁺ transients, and these effects were blocked by atropine or an M3 receptor antagonist (DAU 5884). EFS in the presence of atropine caused inhibition of Ca²⁺ via release of NO. Cessation of nitrergic stimulation resulted in a substantial increase in Ca²⁺ transients, known as post-stimulus excitation. In summary, ICC-MY, important for the generation of propulsive contractions in the colon, are innervated by excitatory (cholinergic) and inhibitory (nitrergic) motor neurons, and these inputs regulate the excitability of these cells.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103082"},"PeriodicalIF":4.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154986","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":"MICU1 attenuates neuronal apoptosis after subarachnoid hemorrhage by inhibiting mitochondrial calcium overload and damage","authors":"Jie Wang ,&nbsp;Yue Cui ,&nbsp;Peng-Fei Ding ,&nbsp;Jia-Tong Zhang ,&nbsp;Xun-Zhi Liu ,&nbsp;Sen Gao ,&nbsp;Xiang-Xin Chen ,&nbsp;Zheng Peng ,&nbsp;Xiao-Jian Li ,&nbsp;Ling-Yun Wu ,&nbsp;Yong-Yue Gao ,&nbsp;Chun-Hua Hang ,&nbsp;Wei Li","doi":"10.1016/j.ceca.2025.103080","DOIUrl":"10.1016/j.ceca.2025.103080","url":null,"abstract":"<div><h3>Background</h3><div>Subarachnoid hemorrhage (SAH) is a severe neurological emergency associated with substantial morbidity and mortality. Research into the mechanisms underlying neuronal injury following SAH has identified early brain injury (EBI) as a critical factor influencing clinical outcomes. Among the various pathological processes involved in EBI, calcium overload remains relatively understudied yet plays a pivotal role in neuronal damage. Excessive accumulation of calcium within mitochondria can initiate apoptotic and autophagic pathways, contributing to cell death. Mitochondrial calcium uptake 1 (MICU1), a regulatory protein located on the inner mitochondrial membrane, functions to modulate mitochondrial calcium ions by inhibiting calcium influx under conditions of low intracellular calcium concentration.</div></div><div><h3>Methods</h3><div>Mitochondria were extracted from the cerebrospinal fluid (CSF) of patients with SAH to evaluate the extent of mitochondrial damage. In vivo and in vitro SAH models were employed to assess mitochondrial damage and dynamic changes in both mitochondrial and cytosolic calcium levels. The interaction between MICU1 and mitochondria was further examined. To investigate the functional role of MICU1, lentivirus vectors were used to upregulate MICU1 expression, while siRNA was applied to knock down its expression in Neuron-2a (N2a) cells. Following hemoglobin (Hb) stimulation, mitochondrial damage and apoptosis were systematically evaluated.</div></div><div><h3>Results</h3><div>Analysis of CSF from SAH patients revealed decreased MICU1 expression and aggravated mitochondrial damage. Hb stimulation of primary neurons and N2a cells led to reduced MICU1 expression and mitochondrial calcium overload, which mediated mitochondrial damage and promoted the progression of neuronal apoptosis. Following upregulation of MICU1 expression in N2a cells, the cells exhibited enhanced tolerance to Hb-induced calcium overload, resulting in a significant reduction in mitochondrial damage. This protective effect was attenuated by MICU1 siRNA treatment. Moreover, MICU1 overexpression alleviated Hb-induced apoptosis in N2a cells, whereas siRNA-mediated knockdown of MICU1 exacerbated apoptotic responses.</div></div><div><h3>Conclusion</h3><div>Mitochondrial calcium overload in neurons following SAH contributes to the development of EBI and neuronal damage. MICU1 exerts a neuroprotective role by mitigating mitochondrial calcium overload, thereby reducing mitochondrial damage and neuronal apoptosis.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103080"},"PeriodicalIF":4.0,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102587","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":"CPVT1 point mutations in RyR2 S5 and S6 segments and their Ca2+ signaling consequence","authors":"Xiao-hua Zhang ,&nbsp;Grace Ellen Donch ,&nbsp;Naohiro Yamaguchi ,&nbsp;Martin Morad","doi":"10.1016/j.ceca.2025.103081","DOIUrl":"10.1016/j.ceca.2025.103081","url":null,"abstract":"<div><div>Precise activation of cardiac ryanodine receptor (RyR2) by small influx of Ca²⁺ during the action potential triggers the release of SR Ca²⁺ that activates contraction, a process known as Ca²⁺-induced Ca²⁺ release (CICR). Missense mutations in RyR2 often cause aberrant and unregulated Ca²⁺ releases that are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), often lethal arrhythmias. Here using CRISPR/Cas9 gene editing in human induced pluripotent stem cells (hiPSCs), we extended our previous studies to include two new arrhythmogenic mutations one, R4822H, located in S5-S6 transmembrane luminal loop near RyR2 selective filter and the other, L4865V, located on S6 segment. TIRF-imaging of voltage-clamped mutant myocytes showed that I_Ca and caffeine-triggered cytosolic Ca²⁺ rise (Fura-2 signal) or ER-GCaMP6 SR Ca²⁺ release signals were significantly suppressed in R4822H but not in L4865V myocytes. Spontaneous Ca²⁺ transients, however, persisted in both mutant lines activating both Fura-2 and ER-GCaMP6 Ca²⁺ transients in L4865V cells, but only Fura-2 Ca²⁺ transients in R4822H mutant. Spontaneous Ca²⁺ sparks igniting frequencies were similar in both mutants, but spark durations were significantly shorter. Although both of these mutations are located at S5 and S6 transmembrane regions of RyR2, their phenotypes diverge markedly. L4865V mutant does not show suppressed E-C coupling function, while R4822H mutant has completely suppressed CICR suggesting that the spontaneous beating in R4822H mutant results from remodeling of dormant Ca²⁺ signaling pathway expressed in hiPSC<img>CMs.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103081"},"PeriodicalIF":4.0,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102592","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":"SERCA3, ubiquitous but specific calcium pumps?","authors":"Maëliss Toth ,&nbsp;Shaymaa Alhabib ,&nbsp;Boris Manoury ,&nbsp;Régis Bobe ,&nbsp;Véronique Leblais","doi":"10.1016/j.ceca.2025.103079","DOIUrl":"10.1016/j.ceca.2025.103079","url":null,"abstract":"<div><div>The calcium ion (Ca²⁺) is an important second messenger for the organism, participating in the regulation of various physiological responses in all cell types. In view of its crucial role, maintaining calcium homeostasis is important. This is why many players tightly regulate calcium homeostasis. These include a type of transporter historically located in the sarcoplasmic or endoplasmic reticulum (SR or ER), called Sarco-Endoplasmic Reticulum Ca²⁺-ATPase or SERCA calcium pumps (Toyoshima et al., 2000). Existence of these pumps was first demonstrated in the 1960s in rabbit skeletal muscle (Ebashi and Lipmann, 1962). In the mid-80s, only two families of these transporters, SERCA1 and SERCA2, were described in the skeletal muscle and the cardiovascular system, respectively. However, the existence of a third family, named SERCA3, was subsequently revealed. In this review, we present an overview of the current knowledge of the SERCA3. We firstly present the structure of this pump from its gene to the protein and its catalytic properties, highlighting its specific features compared to other isoforms. We then focus on the pathophysiological settings by describing its functional role established in several organs and pointing out the studies assuming its implication in different diseases such as obesity or cancers.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103079"},"PeriodicalIF":4.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079624","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":"Dantrolene normalizes heightened Ca2+ influx in activated T cells from the familial Alzheimer's disease TgF344-AD rats","authors":"Navdeep K. Uppal ,&nbsp;Anthony Valenzuela ,&nbsp;Pamela J. Lein ,&nbsp;Alla F. Fomina","doi":"10.1016/j.ceca.2025.103072","DOIUrl":"10.1016/j.ceca.2025.103072","url":null,"abstract":"<div><h3>Aim</h3><div>Dysregulation of the peripheral immune response contributes to Alzheimer's disease pathogenesis. Dantrolene, a negative allosteric modulator of ryanodine receptor types 1 and 3, reduces neurodegeneration in Alzheimer's disease animal models by an unclear mechanism. Given that Alzheimer's disease causative mutations in amyloid precursor and presenilin proteins interfere with intracellular Ca²⁺ signaling in neurons, we tested the hypotheses that these mutations may impair Ca²⁺ signaling in T lymphocytes and that dantrolene can repair this defect.</div></div><div><h3>Methods</h3><div>We explored cytosolic Ca²⁺ dynamics and effects of dantrolene sodium in resting and activated splenic T cells derived from adult transgenic TgF344-AD rats expressing mutant human \"Swedish\" amyloid precursor (APPsw) and presenilin 1 lacking exon 9 (PS1Δ9) proteins, and in control wild-type rats.</div></div><div><h3>Results</h3><div>We found no differences in the cytosolic Ca²⁺ signaling between resting T cells from TgF344-AD and control rats. In contrast, amplitudes of caffeine-triggered calcium transients and store-operated Ca²⁺ entry were significantly larger in activated TgF344-AD rat T cells relative to wild-type rat T cells. Preincubation with dantrolene sodium reduced the amplitude and the rate of Ca²⁺ influx in activated TgF344-AD rat T cells in the absence of store refilling and after dissipation of inner mitochondrial membrane potential, indicating that it does not involve Ca²⁺ release via ryanodine receptors or mitochondrial Ca²⁺ uptake.</div></div><div><h3>Conclusions</h3><div>Expression of Alzheimer's disease risk genes upregulates the store-operated Ca²⁺ entry in T cells, which may alter peripheral immune responses and exacerbate Alzheimer's disease pathogenesis. We speculate that dantrolene's neuroprotective effect in Alzheimer's disease animal models may be due to its normalization of the peripheral T cells' Ca²⁺ signaling and functions.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103072"},"PeriodicalIF":4.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045742","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":"CNO induced Ca2+ store and glutamate-dependent nonspecific Ca2+ signalling in DREADD-free brain slices","authors":"Xiao-Yu Zhang ,&nbsp;Xi Wu ,&nbsp;Rui-yun Bi ,&nbsp;Shan Zhang ,&nbsp;Ye-Hua Gan","doi":"10.1016/j.ceca.2025.103070","DOIUrl":"10.1016/j.ceca.2025.103070","url":null,"abstract":"<div><div>DREADD (design receptors exclusively activated by designer drugs) is a widely used powerful tool designed to study specific cellular functions. However, off-target effects of chemogenetic activators, including clozapine N-oxide (CNO) and deschloroclozapine (DCZ), have been reported. In our study, we demonstrated the direct off-target effects of CNO and DCZ on basal Ca²⁺ levels in the locus coeruleus nucleus in both neurons and astrocytes by combining viral microinjection, Ca²⁺ imaging and electrophysiology. We observed that CNO induced a Ca²⁺ store-dependent increase in basal Ca²⁺ in both DREADD-absent neurons and astrocytes; interestingly, CNO directly increased the frequency of spontaneous presynaptic glutamate release. Furthermore, ionotropic glutamate receptors contributed to the CNO-induced increase in Ca²⁺ in both DREADD-free neurons and astrocytes. Importantly, IP3R2-KO diminished CNO-induced Ca²⁺ raise in astrocytes but not neurons. Our results revealed direct Ca²⁺ store- and glutamate-dependent off-target effects of DREADD agonists during their cellular action, which may help elucidate the mechanisms underlying the off-target effects of chemogenetic tools.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103070"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922709","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":"Silencing CALB1 enhances prostate cancer radiosensitivity via calcium-mediated mitochondrial dysfunction and cellular senescence","authors":"Chen Gong ,&nbsp;Senmao Li ,&nbsp;Ye An ,&nbsp;Chadanfeng Yang ,&nbsp;Zhiyong Tan ,&nbsp;Wujie Chen ,&nbsp;Dihao Lv ,&nbsp;Haichao Wu ,&nbsp;Haifeng Wang ,&nbsp;Shi Fu ,&nbsp;Haihao Li ,&nbsp;Yanjie Kong ,&nbsp;Yinglong Huang ,&nbsp;Mingxia Ding","doi":"10.1016/j.ceca.2025.103071","DOIUrl":"10.1016/j.ceca.2025.103071","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer remains a leading cause of cancer-related deaths in men, with radioresistance limiting treatment efficacy. This study investigates the role of Calbindin 1 (CALB1), a calcium-binding protein regulated by miR-186–5p, in prostate cancer progression and radiation response.</div></div><div><h3>Methods</h3><div>CALB1 expression was analyzed using GEO and TCGA datasets, and the regulatory relationship with miR-186–5p was validated. Functional studies including CALB1 knockdown, calcium chelation, and mitochondrial rescue interventions were conducted in prostate cancer cells, spheroids, and xenograft models, assessing proliferation, senescence, calcium homeostasis, and radiation response.</div></div><div><h3>Results</h3><div>We identified CALB1 as a target of downregulated miR-186–5p in prostate cancer. CALB1 silencing inhibited prostate cancer growth by inducing cellular senescence through calcium dysregulation, mitochondrial dysfunction, and oxidative stress. CALB1 depletion significantly enhanced radiosensitivity both in vitro and in vivo, with calcium chelation or mitochondrial interventions partially rescuing these effects.</div></div><div><h3>Conclusions</h3><div>CALB1 regulates prostate cancer progression and radiation response by maintaining calcium homeostasis. Its depletion triggers calcium overload and mitochondrial dysfunction, enhancing radiation sensitivity and identifying CALB1 as a potential therapeutic target.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"132 ","pages":"Article 103071"},"PeriodicalIF":4.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926570","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}