Pub Date : 2024-10-29DOI: 10.1016/j.ceca.2024.102966
The field of ferroptosis research has grown exponentially since this form of cell death was first identified over a decade ago. Ferroptosis, an iron- and ROS-dependent type of cell death, is controlled by various metabolic pathways, including but not limited to redox and calcium (Ca2+) homeostasis, iron fluxes, mitochondrial function and lipid metabolism. Importantly, therapy-resistant tumors are particularly susceptible to ferroptotic cell death, rendering ferroptosis a promising therapeutic strategy against numerous malignancies. Calcium signals are important regulators of both cancer progression and cell death, with recent studies indicating their involvement in ferroptosis. Cells undergoing ferroptosis are characterized by plasma membrane rupture and the formation of nanopores, which facilitate influx of ions such as Ca2+ into the affected cells. Furthermore, mitochondrial Ca²⁺ levels have been implicated in directly influencing the cellular response to ferroptosis. Despite the remarkable progress made in the field, our understanding of the contribution of Ca2+ signals to ferroptosis remains limited. Here, we summarize key connections between Ca²⁺ signaling and ferroptosis in cancer pathobiology and discuss their potential therapeutic significance.
{"title":"Calcium signals as regulators of ferroptosis in cancer","authors":"","doi":"10.1016/j.ceca.2024.102966","DOIUrl":"10.1016/j.ceca.2024.102966","url":null,"abstract":"<div><div>The field of ferroptosis research has grown exponentially since this form of cell death was first identified over a decade ago. Ferroptosis, an iron- and ROS-dependent type of cell death, is controlled by various metabolic pathways, including but not limited to redox and calcium (Ca<sup>2+</sup>) homeostasis, iron fluxes, mitochondrial function and lipid metabolism. Importantly, therapy-resistant tumors are particularly susceptible to ferroptotic cell death, rendering ferroptosis a promising therapeutic strategy against numerous malignancies. Calcium signals are important regulators of both cancer progression and cell death, with recent studies indicating their involvement in ferroptosis. Cells undergoing ferroptosis are characterized by plasma membrane rupture and the formation of nanopores, which facilitate influx of ions such as Ca<sup>2+</sup> into the affected cells. Furthermore, mitochondrial Ca²⁺ levels have been implicated in directly influencing the cellular response to ferroptosis. Despite the remarkable progress made in the field, our understanding of the contribution of Ca<sup>2+</sup> signals to ferroptosis remains limited. Here, we summarize key connections between Ca²⁺ signaling and ferroptosis in cancer pathobiology and discuss their potential therapeutic significance.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586318","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 : 2024-10-24DOI: 10.1016/j.ceca.2024.102965
{"title":"GPCR signalling: Yet another variant route in a highly complex road map","authors":"","doi":"10.1016/j.ceca.2024.102965","DOIUrl":"10.1016/j.ceca.2024.102965","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552072","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 : 2024-10-23DOI: 10.1016/j.ceca.2024.102962
In a recent publication, Hernansanz-Agusti̒n et al. propose that a sodium gradient across the inner mitochondrial membrane, generated by a Na+/H+ activity integral to Complex I can account for half of the mitochondrial membrane potential. This conflicts with conventional electrophysiological and chemiosmotic understanding.
在最近发表的一篇文章中，Hernansanz-Agusti̒n 等人提出，线粒体内膜上的钠梯度是由与复合体 I 不可分割的 Na+/H+ 活性产生的，可以占线粒体膜电位的一半。这与传统的电生理学和化学渗透理解相冲突。
{"title":"Does a transmembrane sodium gradient control membrane potential in mammalian mitochondria?","authors":"","doi":"10.1016/j.ceca.2024.102962","DOIUrl":"10.1016/j.ceca.2024.102962","url":null,"abstract":"<div><div>In a recent publication, Hernansanz-Agusti̒n et al. propose that a sodium gradient across the inner mitochondrial membrane, generated by a Na<sup>+</sup>/H<sup>+</sup> activity integral to Complex I can account for half of the mitochondrial membrane potential. This conflicts with conventional electrophysiological and chemiosmotic understanding.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564098","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 : 2024-10-21DOI: 10.1016/j.ceca.2024.102964
{"title":"Calcium and chloride out of sync: The role of signaling in Sjögren's salivary gland issues","authors":"","doi":"10.1016/j.ceca.2024.102964","DOIUrl":"10.1016/j.ceca.2024.102964","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495676","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 : 2024-10-20DOI: 10.1016/j.ceca.2024.102960
{"title":"Corrigendum to “Loss-of-function W4645R mutation in the RyR2-caffeine binding site: implications for synchrony and arrhythmogenesis” [Cell Calcium 123 (2024) 102925]","authors":"","doi":"10.1016/j.ceca.2024.102960","DOIUrl":"10.1016/j.ceca.2024.102960","url":null,"abstract":"","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458791","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 : 2024-10-18DOI: 10.1016/j.ceca.2024.102961
Endoplasmic reticulum (ER) stress is triggered upon the interference with oxidative protein folding that aims to produce fully folded, disulfide-bonded and glycosylated proteins, which are then competent to exit the ER. Many of the enzymes catalyzing this process require the binding of Ca2+ ions, including the chaperones BiP/GRP78, calnexin and calreticulin. The induction of ER stress with a variety of drugs interferes with chaperone Ca2+ binding, increases cytosolic Ca2+through the opening of ER Ca2+ channels, and activates store-operated Ca2+ entry (SOCE). Posttranslational modifications (PTMs) of the ER Ca2+ handling proteins through ER stress-dependent phosphorylation or oxidation control these mechanisms, as demonstrated in the case of the sarco/endoplasmic reticulum ATPase (SERCA), inositol 1,4,5 trisphosphate receptors (IP3Rs) or stromal interaction molecule 1 (STIM1). Their aim is to restore ER Ca2+ homeostasis but also to increase Ca2+ transfer from the ER to mitochondria during ER stress. This latter function boosts ER bioenergetics, but also triggers apoptosis if ER Ca2+ signaling persists. ER Ca2+ toolkit oxidative modifications upon ER stress can occur within the ER lumen or in the adjacent cytosol. Enzymes involved in this redox control include ER oxidoreductin 1 (ERO1) or the thioredoxin-family protein disulfide isomerases (PDI) and ERp57. A tight, but adaptive connection between ER Ca2+ content, ER stress and mitochondrial readouts allows for the proper functioning of many tissues, including skeletal muscle, the liver, and the pancreas, where ER stress either maintains or compromises their function, depending on its extent and context. Upon mutation of key regulators of ER Ca2+ signaling, diseases such as muscular defects (e.g., from mutated selenoprotein N, SEPN1/SELENON), or diabetes (e.g., from mutated PERK) are the result.
内质网（ER）应激是在氧化蛋白质折叠受到干扰时引发的，目的是产生完全折叠、二硫键结合和糖基化的蛋白质，然后使其能够离开ER。催化这一过程的许多酶都需要与 Ca2+ 离子结合，其中包括伴侣蛋白 BiP/GRP78、calnexin 和 calreticulin。用多种药物诱导ER应激会干扰伴侣的Ca2+结合，通过打开ER Ca2+通道增加细胞膜Ca2+，并激活贮存操作的Ca2+进入（SOCE）。ER钙离子处理蛋白的翻译后修饰（PTM）是通过ER应激依赖性磷酸化或氧化来控制这些机制的，如肌浆/内质网ATP酶（SERCA）、1,4,5-三磷酸肌醇受体（IP3Rs）或基质相互作用分子1（STIM1）的情况所示。它们的目的是恢复 ER Ca2+ 的平衡，同时在 ER 应激时增加 Ca2+ 从 ER 向线粒体的转移。后一种功能可增强 ER 的生物能，但如果 ER Ca2+ 信号持续存在，也会引发细胞凋亡。ER应激时ER Ca2+工具箱的氧化修饰可发生在ER腔内或邻近的细胞质中。参与这种氧化还原控制的酶包括ER氧化还原蛋白1（ERO1）或硫氧还原蛋白家族的蛋白二硫异构酶（PDI）和ERp57。ER Ca2+ 含量、ER 应激和线粒体读数之间存在着紧密的适应性联系，这使得包括骨骼肌、肝脏和胰腺在内的许多组织都能正常运作。一旦ER Ca2+信号的关键调节因子发生突变，就会导致肌肉缺陷（如硒蛋白N SEPN1/SELENON突变）或糖尿病（如PERK突变）等疾病。
{"title":"ER stress as a sentinel mechanism for ER Ca2+ homeostasis","authors":"","doi":"10.1016/j.ceca.2024.102961","DOIUrl":"10.1016/j.ceca.2024.102961","url":null,"abstract":"<div><div>Endoplasmic reticulum (ER) stress is triggered upon the interference with oxidative protein folding that aims to produce fully folded, disulfide-bonded and glycosylated proteins, which are then competent to exit the ER. Many of the enzymes catalyzing this process require the binding of Ca<sup>2+</sup> ions, including the chaperones BiP/GRP78, calnexin and calreticulin. The induction of ER stress with a variety of drugs interferes with chaperone Ca<sup>2+</sup> binding, increases cytosolic Ca<sup>2+</sup>through the opening of ER Ca<sup>2+</sup> channels, and activates store-operated Ca<sup>2+</sup> entry (SOCE). Posttranslational modifications (PTMs) of the ER Ca<sup>2+</sup> handling proteins through ER stress-dependent phosphorylation or oxidation control these mechanisms, as demonstrated in the case of the sarco/endoplasmic reticulum ATPase (SERCA), inositol 1,4,5 trisphosphate receptors (IP<sub>3</sub>Rs) or stromal interaction molecule 1 (STIM1). Their aim is to restore ER Ca<sup>2+</sup> homeostasis but also to increase Ca<sup>2+</sup> transfer from the ER to mitochondria during ER stress. This latter function boosts ER bioenergetics, but also triggers apoptosis if ER Ca<sup>2+</sup> signaling persists. ER Ca<sup>2+</sup> toolkit oxidative modifications upon ER stress can occur within the ER lumen or in the adjacent cytosol. Enzymes involved in this redox control include ER oxidoreductin 1 (ERO1) or the thioredoxin-family protein disulfide isomerases (PDI) and ERp57. A tight, but adaptive connection between ER Ca<sup>2+</sup> content, ER stress and mitochondrial readouts allows for the proper functioning of many tissues, including skeletal muscle, the liver, and the pancreas, where ER stress either maintains or compromises their function, depending on its extent and context. Upon mutation of key regulators of ER Ca<sup>2+</sup> signaling, diseases such as muscular defects (e.g., from mutated selenoprotein N, SEPN1/SELENON), or diabetes (e.g., from mutated PERK) are the result.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544020","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 : 2024-10-18DOI: 10.1016/j.ceca.2024.102963
The IP3 receptor (IP3R) is a ubiquitously expressed Ca2+-release channel located in the endoplasmic reticulum (ER). Ca2+ signals originating from the IP3R initiate or regulate a plethora of cellular events, including cell life and death processes, e.g. exaggerated Ca2+ release from the ER to the mitochondria is a trigger for apoptosis. Recently, Cho et al. (Current Biology, 2024, DOI: 10.1016/j.cub.2024.08.057) demonstrated that in epithelial monolayers a sustained [Ca2+] elevation caused by the IP3Rs is responsible for the extrusion of adjacent apoptotic cells out of the epithelial monolayer. Interestingly, the IP3Rs involved are associated with the desmosomes via K-Ras-induced actin-interacting protein (KRAP). This study not only highlight a novel role of the IP3R in apoptosis, but also shed a new light on how KRAP -and by extension KRAP-related proteins- contribute to the regulation of IP3R activity and, more broadly, underscores the crucial role of associated proteins in determining the function of IP3Rs.
{"title":"The IP3 receptor-KRAP complex at the desmosomes: A new player in the apoptotic process","authors":"","doi":"10.1016/j.ceca.2024.102963","DOIUrl":"10.1016/j.ceca.2024.102963","url":null,"abstract":"<div><div>The IP<sub>3</sub> receptor (IP<sub>3</sub>R) is a ubiquitously expressed Ca<sup>2+</sup>-release channel located in the endoplasmic reticulum (ER). Ca<sup>2+</sup> signals originating from the IP<sub>3</sub>R initiate or regulate a plethora of cellular events, including cell life and death processes, e.g. exaggerated Ca<sup>2+</sup> release from the ER to the mitochondria is a trigger for apoptosis. Recently, Cho et al. (Current Biology, 2024, DOI: 10.1016/j.cub.2024.08.057) demonstrated that in epithelial monolayers a sustained [Ca<sup>2+</sup>] elevation caused by the IP<sub>3</sub>Rs is responsible for the extrusion of adjacent apoptotic cells out of the epithelial monolayer. Interestingly, the IP<sub>3</sub>Rs involved are associated with the desmosomes via K-Ras-induced actin-interacting protein (KRAP). This study not only highlight a novel role of the IP<sub>3</sub>R in apoptosis, but also shed a new light on how KRAP -and by extension KRAP-related proteins- contribute to the regulation of IP<sub>3</sub>R activity and, more broadly, underscores the crucial role of associated proteins in determining the function of IP<sub>3</sub>Rs.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495677","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 : 2024-10-08DOI: 10.1016/j.ceca.2024.102959
Fluctuations in mitochondrial matrix Ca2+ plays a critical role in matching energy production to cellular demand through direct effects on oxidative phosphorylation and ATP production. Disruption in mitochondrial Ca2+ homeostasis, particularly under pathological conditions such as ischemia or heart failure, can lead to mitochondrial dysfunction, energy deficit, and eventually death of cardiomyocytes. The primary channel regulating acute mitochondrial Ca2+ influx is the mitochondrial Ca2+ uniporter (mtCU), which is regulated by the mitochondrial Ca2+ uptake (MICU) proteins that were examined here.
{"title":"MICU1 and MICU2, two peas in a pod or entirely different fruits?","authors":"","doi":"10.1016/j.ceca.2024.102959","DOIUrl":"10.1016/j.ceca.2024.102959","url":null,"abstract":"<div><div>Fluctuations in mitochondrial matrix Ca<sup>2+</sup> plays a critical role in matching energy production to cellular demand through direct effects on oxidative phosphorylation and ATP production. Disruption in mitochondrial Ca<sup>2+</sup> homeostasis, particularly under pathological conditions such as ischemia or heart failure, can lead to mitochondrial dysfunction, energy deficit, and eventually death of cardiomyocytes. The primary channel regulating acute mitochondrial Ca<sup>2+</sup> influx is the mitochondrial Ca<sup>2+</sup> uniporter (mtCU), which is regulated by the mitochondrial Ca<sup>2+</sup> uptake (MICU) proteins that were examined here.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433063","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 : 2024-10-05DOI: 10.1016/j.ceca.2024.102958
Mitochondrial Ca2+ plays a positive role in regulating pyruvate dehydrogenase, as well as the TCA cycle enzymes isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. This regulation boosts the production of reducing equivalents that fuel the electron transport chain, ultimately driving ATP production. The Mitochondrial Calcium Uniporter (MCU) is the highly selective channel responsible for mitochondrial Ca2+ uptake when local Ca2+ levels reach the threshold for channel activation. In a recent study, LaMoia et al. used an innovative [13C5]glutamine-based metabolic flux analysis method (Q-flux) to measure in vivo hepatic metabolic fluxes in liver-specific MCU-/- mice. Surprisingly, they observed increased flux through isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. Metabolic pathways are continuously reorganized in response to intrinsic cellular signals, as well as hormonal and nutritional inputs. Integrating metabolic flux analysis into complex systems can provide deeper insights into how metabolic adaptations occur under different conditions.
{"title":"The intricacies of mitochondrial calcium and enzyme regulation in liver metabolism","authors":"","doi":"10.1016/j.ceca.2024.102958","DOIUrl":"10.1016/j.ceca.2024.102958","url":null,"abstract":"<div><div>Mitochondrial Ca<sup>2+</sup> plays a positive role in regulating pyruvate dehydrogenase, as well as the TCA cycle enzymes isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. This regulation boosts the production of reducing equivalents that fuel the electron transport chain, ultimately driving ATP production. The Mitochondrial Calcium Uniporter (MCU) is the highly selective channel responsible for mitochondrial Ca<sup>2+</sup> uptake when local Ca<sup>2+</sup> levels reach the threshold for channel activation. In a recent study, LaMoia et al. used an innovative [<sup>13</sup>C<sub>5</sub>]glutamine-based metabolic flux analysis method (Q-flux) to measure in vivo hepatic metabolic fluxes in liver-specific MCU<sup>-/-</sup> mice. Surprisingly, they observed increased flux through isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. Metabolic pathways are continuously reorganized in response to intrinsic cellular signals, as well as hormonal and nutritional inputs. Integrating metabolic flux analysis into complex systems can provide deeper insights into how metabolic adaptations occur under different conditions.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406164","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 : 2024-09-25DOI: 10.1016/j.ceca.2024.102957
TRP Vanilloid 1 (TRPV1) channel, one of the major members of the TRP family was discovered to play a critical role in pain sensation, particularly inflammatory pain, and is associated with hyperalgesia, an enhanced sensitivity to pain. A new study by Fanet al.“Structural basis of TRPV1 inhibition by SAF312 and cholesterol” sheds new light on the mechanistic structural basis of TRPV1 inhibition by SAF312 (Libvatrep), a TRPV1 antagonist, currently in phase II clinical trials. They discover that the binding site of SAF312 in TRPV1 is in close vicinity and partially overlaps with the binding site of cholesterol and that removal of cholesterol interferes with the ability of SAF312 to suppress TRPV1 current.
{"title":"Inhibition of TRPV1 by an antagonist in clinical trials is dependent on cholesterol binding","authors":"","doi":"10.1016/j.ceca.2024.102957","DOIUrl":"10.1016/j.ceca.2024.102957","url":null,"abstract":"<div><div>TRP Vanilloid 1 (TRPV1) channel, one of the major members of the TRP family was discovered to play a critical role in pain sensation, particularly inflammatory pain, and is associated with hyperalgesia, an enhanced sensitivity to pain. A new study by <em><u>Fan</u></em> <u>et al.</u> <em><u>“</u><u>Structural basis of TRPV1 inhibition by SAF312 and cholesterol</u></em>” sheds new light on the mechanistic structural basis of TRPV1 inhibition by SAF312 (Libvatrep), a TRPV1 antagonist, currently in phase II clinical trials. They discover that the binding site of SAF312 in TRPV1 is in close vicinity and partially overlaps with the binding site of cholesterol and that removal of cholesterol interferes with the ability of SAF312 to suppress TRPV1 current.</div></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364555","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}
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