Pub Date : 2025-04-16DOI: 10.1016/j.ceca.2025.103031
Shi-Li Zhou , Lan-Lan Zhong , Yi-Lan Wu , Si-Wen Ji , Yong Li , Na Niu
Ion channels, membrane proteins that facilitate the transport of various inorganic ions across hydrophobic cellular lipid membranes, are ubiquitous in a wide variety of cell and tissue types. They are involved in establishing the cell membrane potential and play a role in various physiological activities by regulating ion concentrations within the cell. Dendritic cells (DCs) are specialised antigen-presenting cells found mainly on the surface of the body (skin and mucous membranes), in the mesenchyme of most organs, in the T-cell compartment of the spleen and in lymph nodes. DCs exert an important influence on the regulation of inflammation by activating T cells and producing cytokines. Studies have shown that ion channels expressed in DCs contribute to the regulation of the immune response, making them a key component of the immune system. This review summarises the major scientific advances in understanding the functional impact of ion channels (calcium channels, sodium channels and aquaporin) in DCs, including the regulation of inflammatory responses, antigen presentation, maturation, migration and cytokine production, to inform ongoing studies of ion channel function in DCs.
{"title":"The role of ion channels in the regulation of dendritic cell function","authors":"Shi-Li Zhou , Lan-Lan Zhong , Yi-Lan Wu , Si-Wen Ji , Yong Li , Na Niu","doi":"10.1016/j.ceca.2025.103031","DOIUrl":"10.1016/j.ceca.2025.103031","url":null,"abstract":"<div><div>Ion channels, membrane proteins that facilitate the transport of various inorganic ions across hydrophobic cellular lipid membranes, are ubiquitous in a wide variety of cell and tissue types. They are involved in establishing the cell membrane potential and play a role in various physiological activities by regulating ion concentrations within the cell. Dendritic cells (DCs) are specialised antigen-presenting cells found mainly on the surface of the body (skin and mucous membranes), in the mesenchyme of most organs, in the T-cell compartment of the spleen and in lymph nodes. DCs exert an important influence on the regulation of inflammation by activating T cells and producing cytokines. Studies have shown that ion channels expressed in DCs contribute to the regulation of the immune response, making them a key component of the immune system. This review summarises the major scientific advances in understanding the functional impact of ion channels (calcium channels, sodium channels and aquaporin) in DCs, including the regulation of inflammatory responses, antigen presentation, maturation, migration and cytokine production, to inform ongoing studies of ion channel function in DCs.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103031"},"PeriodicalIF":4.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848346","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}
Pub Date : 2025-04-08DOI: 10.1016/j.ceca.2025.103017
Kriti Ahuja, Rajender K. Motiani
Mitochondria are robust signaling organelle that regulate a variety of cellular functions. One of the key mechanisms that drive mitochondrial signaling is inter-organelle crosstalk. Mitochondria communicates with other organelles primarily via exchange of calcium (Ca2+), reactive oxygen species (ROS) and lipids across organelle membranes. Mitochondria has its own genome but a majority of mitochondrial proteins are encoded by nuclear genome. Therefore, several mitochondrial functions are controlled by nucleus via anterograde signaling. However, the role of mitochondria in driving expression of genes encoded by nuclear genome has recently gained attention. Recent studies from independent groups have demonstrated a critical role for mitochondrial Ca2+signaling in stimulating nuclear gene expression. These studies report that inhibition of mitochondrial Ca2+uptake through silencing of Mitochondrial Ca2+Uniporter (MCU) leads to Ca2+oscillations in the cytosol. The rise in cytosolic Ca2+ results in activation of Ca2+ sensitive transcription factors such as NFATs and NF-B. These transcription factors consequently induce expression of their target genes in the nuclear genome. It is important to highlight that these groups used different cell types and elegantly presented a phenomenon that is conserved across various systems. Notably, mitochondrial Ca2+ signaling mediated transcriptional regulation controls diverse cellular functions ranging from B-cell activation, melanogenesis and aging associated inflammation. Future studies on this signaling module would result in better understanding of this axis in human pathophysiology and could lead to development of novel therapeutic strategies.
{"title":"Calcium acts as a critical determinant of mitochondria-nuclear networking driven retrograde signaling","authors":"Kriti Ahuja, Rajender K. Motiani","doi":"10.1016/j.ceca.2025.103017","DOIUrl":"10.1016/j.ceca.2025.103017","url":null,"abstract":"<div><div>Mitochondria are robust signaling organelle that regulate a variety of cellular functions. One of the key mechanisms that drive mitochondrial signaling is inter-organelle crosstalk. Mitochondria communicates with other organelles primarily via exchange of calcium (Ca<sup>2+</sup>), reactive oxygen species (ROS) and lipids across organelle membranes. Mitochondria has its own genome but a majority of mitochondrial proteins are encoded by nuclear genome. Therefore, several mitochondrial functions are controlled by nucleus via anterograde signaling. However, the role of mitochondria in driving expression of genes encoded by nuclear genome has recently gained attention. Recent studies from independent groups have demonstrated a critical role for mitochondrial Ca<sup>2+</sup>signaling in stimulating nuclear gene expression. These studies report that inhibition of mitochondrial Ca<sup>2+</sup>uptake through silencing of Mitochondrial Ca<sup>2+</sup>Uniporter (MCU) leads to Ca<sup>2+</sup>oscillations in the cytosol. The rise in cytosolic Ca<sup>2+</sup> results in activation of Ca<sup>2+</sup> sensitive transcription factors such as NFATs and NF-<span><math><mi>κ</mi></math></span>B. These transcription factors consequently induce expression of their target genes in the nuclear genome. It is important to highlight that these groups used different cell types and elegantly presented a phenomenon that is conserved across various systems. Notably, mitochondrial Ca<sup>2+</sup> signaling mediated transcriptional regulation controls diverse cellular functions ranging from B-cell activation, melanogenesis and aging associated inflammation. Future studies on this signaling module would result in better understanding of this axis in human pathophysiology and could lead to development of novel therapeutic strategies.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"127 ","pages":"Article 103017"},"PeriodicalIF":4.3,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839191","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}
Pub Date : 2025-04-01DOI: 10.1016/j.ceca.2025.103016
Khaled Machaca
Dendritic Ca2+ signaling is critical for neural transmission and signal processing, however the detailed molecular mechanisms have not been elucidated. Using elegant and complementary imaging approaches Benedetti et al. discover a distinctive ER ladder architecture in dendrites and show that precise localization of Ca2+ signaling proteins at endoplasmic reticulum (ER)-plasma membrane (PM) junctions supports integration of Ca2+ signaling along the dendrite.
{"title":"Scaling up neuronal Ca2+, signaling on ER ladders","authors":"Khaled Machaca","doi":"10.1016/j.ceca.2025.103016","DOIUrl":"10.1016/j.ceca.2025.103016","url":null,"abstract":"<div><div>Dendritic Ca<sup>2+</sup> signaling is critical for neural transmission and signal processing, however the detailed molecular mechanisms have not been elucidated. Using elegant and complementary imaging approaches Benedetti et al. discover a distinctive ER ladder architecture in dendrites and show that precise localization of Ca<sup>2+</sup> signaling proteins at endoplasmic reticulum (ER)-plasma membrane (PM) junctions supports integration of Ca<sup>2+</sup> signaling along the dendrite.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"127 ","pages":"Article 103016"},"PeriodicalIF":4.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799197","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}
Pub Date : 2025-03-25DOI: 10.1016/j.ceca.2025.103015
Grecia J. Medina-Terol , Luis Chimal , Saúl Huerta de la Cruz , Guillermo Ávila , Alberto Aranda , David Cruz-Robles , David Centurión , Julio Altamirano , Rocio Rojo , Norma Leticia Gómez-Viquez
Hydrogen sulfide (H2S) has been proposed to play a cardioprotective role, particularly due to its ability to revert left ventricular hypertrophy (LVH) and mitigate cardiac dysfunction in various cardiomyopathies, including hypertensive heart disease. However, the extent to which cardioprotection by H2S involves improvement in Ca2+ handling remains unclear. Although H2S has been reported to influence the function of key Ca2+ handling proteins, most studies have focused on acute administration of H2S donors in isolated cardiomyocytes, rather than in a therapeutic context. In this study, we used a rat model of hypertension induced by abdominal aortic coarctation (AAC) to evaluate the therapeutic potential of NaHS, an H2S donor, on LVH and Ca2+ handling. After 8 weeks of AAC, hypertensive rats developed moderate LVH, which was accompanied by a reduction in both the amplitude and the rate of rise of systolic Ca2+ transients, as well as a decrease in sarcoplasmic reticulum (SR) Ca2+ load. Despite the reduced SR Ca2+ load, the frequency of diastolic Ca2+ sparks remained high, while the incidence and propagation rate of spontaneous Ca2+ waves significantly increased, suggesting enhanced diastolic SR Ca2+ leak, most likely due to hypersensitivity of ryanodine receptors (RyR2) to Ca2+. On the other hand, NaHS administration during the final 4 weeks of AAC reverted both LVH and hypertension, and increased SR Ca2+ reuptake mediated by the SR Ca2+ ATPase (SERCA2a). However, NaHS treatment failed to restore the amplitude and rate of rise of systolic Ca2+ transients or SR Ca2+ load. Furthermore, SR Ca2+ leak might have worsened, since spontaneous Ca2+ waves increased. In conclusion, NaHS treatment does not appear to normalize all Ca2+ handling properties during hypertensive LVH. On the contrary, NaHS may exert an arrhythmogenic effect, likely due to enhanced SERCA2a activity under conditions of unresolved RyR2 Ca2+ hypersensitivity.
{"title":"H2S treatment reverts cardiac hypertrophy and increases SERCA2a activity but does not fully restore cardiac Ca2+ handling in hypertensive rats","authors":"Grecia J. Medina-Terol , Luis Chimal , Saúl Huerta de la Cruz , Guillermo Ávila , Alberto Aranda , David Cruz-Robles , David Centurión , Julio Altamirano , Rocio Rojo , Norma Leticia Gómez-Viquez","doi":"10.1016/j.ceca.2025.103015","DOIUrl":"10.1016/j.ceca.2025.103015","url":null,"abstract":"<div><div>Hydrogen sulfide (H<sub>2</sub>S) has been proposed to play a cardioprotective role, particularly due to its ability to revert left ventricular hypertrophy (LVH) and mitigate cardiac dysfunction in various cardiomyopathies, including hypertensive heart disease. However, the extent to which cardioprotection by H<sub>2</sub>S involves improvement in Ca<sup>2+</sup> handling remains unclear. Although H<sub>2</sub>S has been reported to influence the function of key Ca<sup>2+</sup> handling proteins, most studies have focused on acute administration of H<sub>2</sub>S donors in isolated cardiomyocytes, rather than in a therapeutic context. In this study, we used a rat model of hypertension induced by abdominal aortic coarctation (AAC) to evaluate the therapeutic potential of NaHS, an H<sub>2</sub>S donor, on LVH and Ca<sup>2+</sup> handling. After 8 weeks of AAC, hypertensive rats developed moderate LVH, which was accompanied by a reduction in both the amplitude and the rate of rise of systolic Ca<sup>2+</sup> transients, as well as a decrease in sarcoplasmic reticulum (SR) Ca<sup>2+</sup> load. Despite the reduced SR Ca<sup>2+</sup> load, the frequency of diastolic Ca<sup>2+</sup> sparks remained high, while the incidence and propagation rate of spontaneous Ca<sup>2+</sup> waves significantly increased, suggesting enhanced diastolic SR Ca<sup>2+</sup> leak, most likely due to hypersensitivity of ryanodine receptors (RyR2) to Ca<sup>2+</sup>. On the other hand, NaHS administration during the final 4 weeks of AAC reverted both LVH and hypertension, and increased SR Ca<sup>2+</sup> reuptake mediated by the SR Ca<sup>2+</sup> ATPase (SERCA2a). However, NaHS treatment failed to restore the amplitude and rate of rise of systolic Ca<sup>2+</sup> transients or SR Ca<sup>2+</sup> load. Furthermore, SR Ca<sup>2+</sup> leak might have worsened, since spontaneous Ca<sup>2+</sup> waves increased. In conclusion, NaHS treatment does not appear to normalize all Ca<sup>2+</sup> handling properties during hypertensive LVH. On the contrary, NaHS may exert an arrhythmogenic effect, likely due to enhanced SERCA2a activity under conditions of unresolved RyR2 Ca<sup>2+</sup> hypersensitivity.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103015"},"PeriodicalIF":4.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769152","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}
The homeostasis of cellular reactive oxygen species (ROS) and calcium (Ca2+) are intricately linked. ROS signaling and Ca2+ signaling are reciprocally regulated within cellular microdomains and are crucial for transcription, metabolism and cell function. Tumor cells often highjack ROS and Ca2+ signaling mechanisms to ensure optimal cell survival and tumor progression. Expression and regulation of Ca2+ channels and transporters at the plasma membrane, endoplasmic reticulum, mitochondria and other endomembranes are often altered in tumor cells, and this includes their regulation by ROS and reactive nitrogen species (RNS). Likewise, alterations in cellular Ca2+ levels influence the generation and scavenging of oxidants and thus can alter the redox homeostasis of the cell. This interplay can be either beneficial or detrimental to the cell depending on the localization, duration and levels of ROS and Ca2+ signals. At one end of the spectrum, Ca2+ and ROS/RNS can function as signaling modules while at the other end, lethal surges in these species are associated with cell death. Here, we highlight the interplay between Ca2+ and ROS in cancer progression, emphasize the impact of redox regulation on Ca2+ transport mechanisms, and describe how Ca2+ signaling pathways, in turn, can regulate the cellular redox environment.
{"title":"Crosstalk between calcium and reactive oxygen species signaling in cancer revisited","authors":"Trayambak Pathak , J.Cory Benson , Priscilla W. Tang , Mohamed Trebak , Nadine Hempel","doi":"10.1016/j.ceca.2025.103014","DOIUrl":"10.1016/j.ceca.2025.103014","url":null,"abstract":"<div><div>The homeostasis of cellular reactive oxygen species (ROS) and calcium (Ca<sup>2+</sup>) are intricately linked. ROS signaling and Ca<sup>2+</sup> signaling are reciprocally regulated within cellular microdomains and are crucial for transcription, metabolism and cell function. Tumor cells often highjack ROS and Ca<sup>2+</sup> signaling mechanisms to ensure optimal cell survival and tumor progression. Expression and regulation of Ca<sup>2+</sup> channels and transporters at the plasma membrane, endoplasmic reticulum, mitochondria and other endomembranes are often altered in tumor cells, and this includes their regulation by ROS and reactive nitrogen species (RNS). Likewise, alterations in cellular Ca<sup>2+</sup> levels influence the generation and scavenging of oxidants and thus can alter the redox homeostasis of the cell. This interplay can be either beneficial or detrimental to the cell depending on the localization, duration and levels of ROS and Ca<sup>2+</sup> signals. At one end of the spectrum, Ca<sup>2+</sup> and ROS/RNS can function as signaling modules while at the other end, lethal surges in these species are associated with cell death. Here, we highlight the interplay between Ca<sup>2+</sup> and ROS in cancer progression, emphasize the impact of redox regulation on Ca<sup>2+</sup> transport mechanisms, and describe how Ca<sup>2+</sup> signaling pathways, in turn, can regulate the cellular redox environment.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"127 ","pages":"Article 103014"},"PeriodicalIF":4.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-04DOI: 10.1016/j.ceca.2025.103010
Gilnei Bruno da Silva , Geórgia de Carvalho Braga , Júlia Leão Batista Simões , Margarete Dulce Bagatini , Aniela Pinto Kempka
Mitochondria represent a fundamental structure for cellular homeostasis, controlling multiple conditions regarding energetic functions and cellular survival. To maintain these organelles functioning in ideal conditions, their membranes count with ion channels for different inorganic ions, which must be balanced to offer the proper function for both the organelle and the cell. However, studies have shown that other health conditions impair the activities of mitochondrial ion channels, including cancer. In this sense, the altered activities of potassium, calcium, and calcium-activated potassium channels are mainly linked with cancer development and cellular homeostasis alteration, demonstrating their role as pharmacological targets. With that in mind, scientists have found significant mitochondrial and cellular responses related to apoptosis and reduction of cellular survival from cells with modulated ion channels, indicating the potential of this possible therapy in carcinogenic contexts. Nonetheless, few studies still evaluate mitochondrial ion channel modulation as a treatment against cancer. Hence, more research must be conducted on this subject.
{"title":"Mitochondrial dysfunction and carcinogenesis: The engagement of ion channels in cancer development","authors":"Gilnei Bruno da Silva , Geórgia de Carvalho Braga , Júlia Leão Batista Simões , Margarete Dulce Bagatini , Aniela Pinto Kempka","doi":"10.1016/j.ceca.2025.103010","DOIUrl":"10.1016/j.ceca.2025.103010","url":null,"abstract":"<div><div>Mitochondria represent a fundamental structure for cellular homeostasis, controlling multiple conditions regarding energetic functions and cellular survival. To maintain these organelles functioning in ideal conditions, their membranes count with ion channels for different inorganic ions, which must be balanced to offer the proper function for both the organelle and the cell. However, studies have shown that other health conditions impair the activities of mitochondrial ion channels, including cancer. In this sense, the altered activities of potassium, calcium, and calcium-activated potassium channels are mainly linked with cancer development and cellular homeostasis alteration, demonstrating their role as pharmacological targets. With that in mind, scientists have found significant mitochondrial and cellular responses related to apoptosis and reduction of cellular survival from cells with modulated ion channels, indicating the potential of this possible therapy in carcinogenic contexts. Nonetheless, few studies still evaluate mitochondrial ion channel modulation as a treatment against cancer. Hence, more research must be conducted on this subject.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103010"},"PeriodicalIF":4.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552733","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}
Pub Date : 2025-02-27DOI: 10.1016/j.ceca.2025.103013
Tam Nguyen , Zhihong Lin , Nirav Dhanesha , Rakesh B. Patel , Mallorie Lane , Grant C. Walters , Leonid P. Shutov , Stefan Strack , Anil K. Chauhan , Yuriy M. Usachev
Mitochondrial Ca2+ transport regulates many neuronal functions including synaptic transmission, ATP production, gene expression and neuronal survival. The mitochondrial Ca2+ uniporter (MCU) is the core molecular component of the mitochondrial Ca2+ uptake complex in the inner mitochondrial membrane. MCUb is a paralog of MCU that negatively regulates mitochondrial Ca2+ uptake in the heart and the cells of the immune system. However, the function of MCUb in the brain is largely unknown. Here, we report that MCUb knockout (KO) led to enhanced mitochondrial Ca2+ uptake in cortical neurons. By simultaneously monitoring changes in cytosolic and mitochondrial Ca2+ concentrations, [Ca2+]cyt and [Ca2+]mt, respectively, we also found that MCUb KO reduced the [Ca2+]cyt threshold required to induce mitochondrial uptake in cortical neurons during electrical stimulation. Exposure of cortical neurons to toxic concentrations of glutamate led to a collapse of mitochondrial membrane potential (ΔΨmt) and [Ca2+]cyt deregulation, and MCUb deletion accelerated the development of both events. Furthermore, using the middle cerebral artery occlusion (MCAO) as a model of transient ischemic stroke in mice, we found that MCUb KO significantly increased MCAO-induced brain damage in male, but not female mice. These results suggest that MCUb regulates neuronal Ca2+ dynamics and excitotoxicity and reveal a sex-dependent role of MCUb in controlling resistance to brain damage following ischemic stroke.
{"title":"Mitochondrial Ca2+ uniporter b (MCUb) regulates neuronal Ca2+ dynamics and resistance to ischemic stroke","authors":"Tam Nguyen , Zhihong Lin , Nirav Dhanesha , Rakesh B. Patel , Mallorie Lane , Grant C. Walters , Leonid P. Shutov , Stefan Strack , Anil K. Chauhan , Yuriy M. Usachev","doi":"10.1016/j.ceca.2025.103013","DOIUrl":"10.1016/j.ceca.2025.103013","url":null,"abstract":"<div><div>Mitochondrial Ca<sup>2+</sup> transport regulates many neuronal functions including synaptic transmission, ATP production, gene expression and neuronal survival. The mitochondrial Ca<sup>2+</sup> uniporter (MCU) is the core molecular component of the mitochondrial Ca<sup>2+</sup> uptake complex in the inner mitochondrial membrane. MCUb is a paralog of MCU that negatively regulates mitochondrial Ca<sup>2+</sup> uptake in the heart and the cells of the immune system. However, the function of MCUb in the brain is largely unknown. Here, we report that MCUb knockout (KO) led to enhanced mitochondrial Ca<sup>2+</sup> uptake in cortical neurons. By simultaneously monitoring changes in cytosolic and mitochondrial Ca<sup>2+</sup> concentrations, [Ca<sup>2+</sup>]<sub>cyt</sub> and [Ca<sup>2+</sup>]<sub>mt</sub>, respectively, we also found that MCUb KO reduced the [Ca<sup>2+</sup>]<sub>cyt</sub> threshold required to induce mitochondrial uptake in cortical neurons during electrical stimulation. Exposure of cortical neurons to toxic concentrations of glutamate led to a collapse of mitochondrial membrane potential (ΔΨ<sub>mt</sub>) and [Ca<sup>2+</sup>]<sub>cyt</sub> deregulation, and MCUb deletion accelerated the development of both events. Furthermore, using the middle cerebral artery occlusion (MCAO) as a model of transient ischemic stroke in mice, we found that MCUb KO significantly increased MCAO-induced brain damage in male, but not female mice. These results suggest that MCUb regulates neuronal Ca<sup>2+</sup> dynamics and excitotoxicity and reveal a sex-dependent role of MCUb in controlling resistance to brain damage following ischemic stroke.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"128 ","pages":"Article 103013"},"PeriodicalIF":4.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578745","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}
Pub Date : 2025-02-15DOI: 10.1016/j.ceca.2025.103002
Barbara A. Niemeyer , David I. Yule
{"title":"Changing of the guards while steering a familiar course","authors":"Barbara A. Niemeyer , David I. Yule","doi":"10.1016/j.ceca.2025.103002","DOIUrl":"10.1016/j.ceca.2025.103002","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"126 ","pages":"Article 103002"},"PeriodicalIF":4.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436889","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}
Pub Date : 2025-02-07DOI: 10.1016/j.ceca.2025.103000
Jacob D. Cunningham, Taylor A. Phillips, Jaroslava Seflova, Ellen E. Cho, Seth L. Robia
To determine how regulation of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) affects the Ca2+ content of the endoplasmic reticulum (ER), we developed a ratiometric ER-localized Ca2+ indicator to rapidly quantify Ca2+ stores and assess SERCA function in live cells. This assay enables screening of membrane micropeptides and small molecules that modulate SERCA and Na+/K+-ATPase activity and may facilitate development of therapies that target cellular Ca2+ handling. Of the micropeptides tested, phospholamban (PLB) had the greatest degree of inhibition of SERCA, as measured by a decrease in ER Ca2+ content compared to control. Sarcolipin (SLN), endoregulin (ELN), and another-regulin (ALN) also decreased ER Ca2+ content, though less potently than PLB. We also investigated micropeptides that have been shown to have a positive effect on ER Ca2+ uptake. Dwarf open reading frame (DWORF), a positive modulator of SERCA activity, and phospholemman (PLM), an inhibitor of the Na+/K+-ATPase, both increased ER Ca2+ content compared to control. A superinhibitory variant of PLM, R70C, further increased ER Ca2+ load compared to wild type PLM. Overall, our findings indicate that the inhibitory potency of micropeptides is governed by their relative binding affinities to SERCA. This allows for finely tuned modulation of Ca2+ handling in different tissues based on differential expressions of micropeptide species. Understanding the contribution of each micropeptide to SERCA regulation may reveal novel strategies for therapeutic intervention in conditions where calcium dysregulation plays a role, such as heart disease, vascular disease, or neurodegenerative disorders.
{"title":"Rapid quantification of intracellular calcium stores reveals effects of membrane micropeptides on SERCA function","authors":"Jacob D. Cunningham, Taylor A. Phillips, Jaroslava Seflova, Ellen E. Cho, Seth L. Robia","doi":"10.1016/j.ceca.2025.103000","DOIUrl":"10.1016/j.ceca.2025.103000","url":null,"abstract":"<div><div>To determine how regulation of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) affects the Ca<sup>2+</sup> content of the endoplasmic reticulum (ER), we developed a ratiometric ER-localized Ca<sup>2+</sup> indicator to rapidly quantify Ca<sup>2+</sup> stores and assess SERCA function in live cells. This assay enables screening of membrane micropeptides and small molecules that modulate SERCA and Na<sup>+</sup>/K<sup>+</sup>-ATPase activity and may facilitate development of therapies that target cellular Ca<sup>2+</sup> handling. Of the micropeptides tested, phospholamban (PLB) had the greatest degree of inhibition of SERCA, as measured by a decrease in ER Ca<sup>2+</sup> content compared to control. Sarcolipin (SLN), endoregulin (ELN), and another-regulin (ALN) also decreased ER Ca<sup>2+</sup> content, though less potently than PLB. We also investigated micropeptides that have been shown to have a positive effect on ER Ca<sup>2+</sup> uptake. Dwarf open reading frame (DWORF), a positive modulator of SERCA activity, and phospholemman (PLM), an inhibitor of the Na<sup>+</sup>/K<sup>+</sup>-ATPase, both increased ER Ca<sup>2+</sup> content compared to control. A superinhibitory variant of PLM, R70C, further increased ER Ca<sup>2+</sup> load compared to wild type PLM. Overall, our findings indicate that the inhibitory potency of micropeptides is governed by their relative binding affinities to SERCA. This allows for finely tuned modulation of Ca<sup>2+</sup> handling in different tissues based on differential expressions of micropeptide species. Understanding the contribution of each micropeptide to SERCA regulation may reveal novel strategies for therapeutic intervention in conditions where calcium dysregulation plays a role, such as heart disease, vascular disease, or neurodegenerative disorders.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"126 ","pages":"Article 103000"},"PeriodicalIF":4.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367809","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}
Pub Date : 2025-02-01DOI: 10.1016/j.ceca.2025.103001
Boris Lavanderos , Maria Paz Saldias , Scott Earley
Brain capillaries contribute to neurovascular coupling (NVC) by sensing neural activity and coordinating upstream arteriole dilation. However, the mechanisms underlying conducted vasodilation remain incompletely understood. Recent findings (PNAS, 2024) identify a novel process, “electrocalcium coupling,” in which hyperpolarizing signals from K+ channels drive long-range Ca²⁺ signaling in capillaries, revealing new insights into the integration of vasodilatory signals in the brain.
{"title":"Shocking insights for neurovascular coupling: Electrical signals ignite calcium dynamics in brain capillaries","authors":"Boris Lavanderos , Maria Paz Saldias , Scott Earley","doi":"10.1016/j.ceca.2025.103001","DOIUrl":"10.1016/j.ceca.2025.103001","url":null,"abstract":"<div><div>Brain capillaries contribute to neurovascular coupling (NVC) by sensing neural activity and coordinating upstream arteriole dilation. However, the mechanisms underlying conducted vasodilation remain incompletely understood. Recent findings (<em>PNAS</em>, 2024) identify a novel process, “electrocalcium coupling,” in which hyperpolarizing signals from K<sup>+</sup> channels drive long-range Ca²⁺ signaling in capillaries, revealing new insights into the integration of vasodilatory signals in the brain.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":"126 ","pages":"Article 103001"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363765","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号