Biochimica et biophysica acta. Molecular cell research最新文献_第3页

The late stages of yeast mitoribosome large subunit biogenesis 酵母线粒体大亚基生物发生的后期

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-25 DOI: 10.1016/j.bbamcr.2025.120051

Sorbhi Rathore , Julian Conrad , Dasmanthie De Silva , Alberto Ferrari , Danielle Bouquio , Hyung-Jun Kim , Roger Salvatori , Andreas Linden , Olexandr Dybkov , Henning Urlaub , Martin Ott , Antoni Barrientos

{"title":"The late stages of yeast mitoribosome large subunit biogenesis","authors":"Sorbhi Rathore , Julian Conrad , Dasmanthie De Silva , Alberto Ferrari , Danielle Bouquio , Hyung-Jun Kim , Roger Salvatori , Andreas Linden , Olexandr Dybkov , Henning Urlaub , Martin Ott , Antoni Barrientos","doi":"10.1016/j.bbamcr.2025.120051","DOIUrl":"10.1016/j.bbamcr.2025.120051","url":null,"abstract":"<div><div>The <em>Saccharomyces cerevisiae</em> mitoribosome synthesizes eight mitochondrial DNA-encoded proteins essential for oxidative phosphorylation. Mitoribosome large subunit (mtLSU) biogenesis involves the conserved DEAD-box helicase Mrh4 and the GTPases Mtg1/GTPBP7 and Mtg2/GTPBP5. Here, we have employed genetic, biochemical, in vitro reconstitution, and cryo-EM approaches to elucidate their hierarchical action during the late stages of mtLSU assembly. We show that Mrh4-mediated bL33m incorporation precedes Mtg1 recruitment to the 21S rRNA. Cryo-EM structures of mitoribosome assembly intermediates accumulating in the absence of Mtg1 or uL16m reveal that Mtg1 restructures the 21S rRNA H73-75 and H93 domains to their mature fold. This subsequently allows the structuring of neighboring peptidyl transfer center region helices and the incorporation of uL6m, uL16m, bL35m, and bL36m during late mtLSU maturation. Unexpectedly, monosomes containing immature mtLSU assemble in Mrh4-, bL33m-, uL16m-, Mtg1-, and Mtg2-depleted mitochondria, at levels that increase with the maturation state of the mtLSU particle. Our data have shed light on the rRNA folding events and the structuring of the MRPs that occur during the late stages of assembly. They have provided insight into the roles of assembly factors Mrh4, Mtg1, and Mtg2 during the process and revealed evolutionarily conserved mechanisms underlying mitochondrial ribosome assembly.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120051"},"PeriodicalIF":3.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925553","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}

引用次数: 0

Multiple roles of EML1 in microtubule stabilization and vesicle transport in the nervous system EML1在神经系统微管稳定和囊泡运输中的多重作用

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-24 DOI: 10.1016/j.bbamcr.2025.120048

Yufang Zhang , Jing Yu , Yao Zhou , Yan Yue , Yan Liu

{"title":"Multiple roles of EML1 in microtubule stabilization and vesicle transport in the nervous system","authors":"Yufang Zhang , Jing Yu , Yao Zhou , Yan Yue , Yan Liu","doi":"10.1016/j.bbamcr.2025.120048","DOIUrl":"10.1016/j.bbamcr.2025.120048","url":null,"abstract":"<div><div>Microtubule-associated protein EML1 is an important member of the EML family and plays a key role in cytoskeleton regulation and neural development. During neural development, EML1 expression is spatiotemporally specific, and its functional abnormalities are closely associated with neural developmental disorders such as subcortical band heterotopia. This article systematically reviews the structural characteristics and biological functions of EML1. Structural studies have shown that EML1 contains unique HELP-WD and TAPE domains, which underlie its binding to microtubules and functional performance. Functionally, EML1 regulates microtubule stability through multiple mechanisms. Moreover, EML1 is also involved in regulating intracellular material transport—maintaining the stability of transport tracks, coordinating the function of motor proteins, and regulating Golgi-related transport. These findings reveal the multiple roles of EML1 in cellular physiological processes and provide a new perspective for understanding the pathogenesis of related diseases. Future research should focus on elucidating the precise EML1 action mechanisms and its potential as a therapeutic target.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120048"},"PeriodicalIF":3.7,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896506","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}

引用次数: 0

CHIP modulates Wnt/β-catenin signalling in colorectal cancer through proteasomal degradation of DDX17 CHIP通过蛋白酶体降解DDX17调节结直肠癌中Wnt/β-catenin信号

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-22 DOI: 10.1016/j.bbamcr.2025.120049

Sunny Kumar , Sayani Ghosh , Malini Basu , Mrinal K. Ghosh

{"title":"CHIP modulates Wnt/β-catenin signalling in colorectal cancer through proteasomal degradation of DDX17","authors":"Sunny Kumar , Sayani Ghosh , Malini Basu , Mrinal K. Ghosh","doi":"10.1016/j.bbamcr.2025.120049","DOIUrl":"10.1016/j.bbamcr.2025.120049","url":null,"abstract":"<div><div>The C-terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase, plays a pivotal role in cellular protein homeostasis by targeting client proteins for proteasomal degradation. DEAD-box RNA helicase DDX17 is a key regulator of RNA metabolism and has been implicated in various cancer-related processes, including Wnt/β-catenin signalling and EMT. In this study, we uncover a novel regulatory axis involving CHIP and DDX17 responsible for modulation of Wnt/β-catenin signalling in colorectal cancer (CRC). Bioinformatic analyses of CPTAC database and immunohistochemical analysis of clinical samples revealed a significant negative correlation between CHIP and DDX17. By using immunoprecipitation-mass spectrometry we have identified DDX17 as a high-confidence interacting partner of CHIP, which was validated through co-immunoprecipitation, domain-mapping, immunocytochemistry, and molecular docking studies, pinpointing the TPR domain of CHIP is essential for this interaction. Mechanistically, CHIP overexpression led to accelerated degradation of DDX17, resulting in reduced β-catenin mRNA stability, leading to the suppression of Wnt/β-catenin signalling that results in G1 arrest and decreasing proliferation and EMT. Conversely, CHIP knockdown stabilized DDX17, hence promoting β-catenin signalling that leads to oncogenic phenotype. Our results suggest that CHIP exerts a tumor-suppressive phenotype in CRC by destruction of DDX17, thereby attenuating β-catenin-driven oncogenic processes. Altogether, this study identifies a novel “CHIP–DDX17–β-catenin” axis as a critical regulatory mechanism in CRC.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120049"},"PeriodicalIF":3.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916654","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}

引用次数: 0

E3 ligase SMURF2 alleviated intrauterine adhesion by stabilizing SMAD6 E3连接酶SMURF2通过稳定SMAD6减轻宫内粘连。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-16 DOI: 10.1016/j.bbamcr.2025.120045

Ke Zhou , Yun Chen , Lishi Chen , Zhenfu Wu , Lirong Zhang , Jingjing Zheng , Song Tian , Mingzhu Wen , Xin Li , Huihua Cai

{"title":"E3 ligase SMURF2 alleviated intrauterine adhesion by stabilizing SMAD6","authors":"Ke Zhou , Yun Chen , Lishi Chen , Zhenfu Wu , Lirong Zhang , Jingjing Zheng , Song Tian , Mingzhu Wen , Xin Li , Huihua Cai","doi":"10.1016/j.bbamcr.2025.120045","DOIUrl":"10.1016/j.bbamcr.2025.120045","url":null,"abstract":"<div><div>Intrauterine adhesion (IUA) is a debilitating uterine disorder characterized by endometrial fibrosis and infertility, for which effective treatments remain limited. Here, we identify the E3 ubiquitin ligase SMURF2 as a critical protective factor against IUA progression. SMURF2 expression was significantly upregulated in endometrial tissues of IUA patients, a murine IUA model, and TGF-β1-treated human endometrial stromal cells (HESCs). Functional analyses revealed that SMURF2 overexpression mitigated fibrosis-associated phenotypes, including enhanced cell proliferation, migration, and extracellular matrix accumulation, both <em>in vitro</em> and <em>in vivo</em>, whereas SMURF2 knockdown had the opposite effect. Mechanistically, SMURF2 directly interacted with the inhibitory SMAD protein SMAD6 and promoted its stabilization via K63-linked polyubiquitination. Mutation analysis confirmed that disruption of the K63 linkage markedly reduced SMAD6 ubiquitination and destabilized the protein. As a result, SMAD6 accumulation suppressed TGF-β/Smad signaling and downstream fibrotic gene expression. These findings reveal a previously unrecognized SMURF2–SMAD6 axis that counteracts endometrial fibrosis, and suggest that enhancing SMURF2-mediated K63-linked ubiquitination may offer a novel therapeutic avenue for IUA treatment.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120045"},"PeriodicalIF":3.7,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871190","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}

引用次数: 0

Calcium-dependent regulation of physiological vs pathological cardiomyocyte hypertrophy 生理性与病理性心肌细胞肥大的钙依赖性调节。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-15 DOI: 10.1016/j.bbamcr.2025.120046

Joshua Chung , Nathan Isles , Stuart Johnston , David J. Collins , Julie R. McMullen , H. Llewelyn Roderick , Vijay Rajagopal

{"title":"Calcium-dependent regulation of physiological vs pathological cardiomyocyte hypertrophy","authors":"Joshua Chung , Nathan Isles , Stuart Johnston , David J. Collins , Julie R. McMullen , H. Llewelyn Roderick , Vijay Rajagopal","doi":"10.1016/j.bbamcr.2025.120046","DOIUrl":"10.1016/j.bbamcr.2025.120046","url":null,"abstract":"<div><div>Cardiomyocyte hypertrophic growth contributes to the adaptative response of the heart to meet sustained increases in hemodynamic demand. While hypertrophic responses to physiological cues maintains or enhances cardiac function, when triggered by pathological cues, this response is maladaptive, associated with compromised heart function, although initially, this response maybe adaptive with preserved function. Since cues and activated pathways associated with both forms of hypertrophy overlap, the question arises as to the mechanism that determines these different outcomes. Here we evaluate the hypothesis that cardiomyocyte Ca<sup>2+</sup> signalling – a regulator of pathological hypertrophy – also signals physiological hypertrophy. We discuss how different Ca<sup>2+</sup> profiles, in distinct subcellular organelles/microdomains, and interacting with other signalling pathways, provide a mechanism for Ca<sup>2+</sup> to be decoded to induce distinct hypertrophic phenotypes. We discuss how integration of computational with rich structural and functional cellular measurements can be used to decipher the role of Ca<sup>2+</sup> in hypertrophic gene programming.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120046"},"PeriodicalIF":3.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871189","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}

引用次数: 0

Corrigendum to "A fluorescent protein C-terminal fusion knock-in is functional with TRPA1 but not TRPC5" [Biochim. Biophys. Acta Mol. Cell Res. 1872(2) (2025) 119887]. “一种荧光蛋白c端融合敲入对TRPA1起作用，但对TRPC5不起作用”的更正[biochem]。Biophys。分子细胞学报，1872(2)(2025)[19887]。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-14 DOI: 10.1016/j.bbamcr.2025.120042

Aaron Tragl, Alexandra Ptakova, Viktor Sinica, Rathej Meerupally, Christine König, Carolina Roza, Ivan Barvík, Viktorie Vlachova, Katharina Zimmermann

引用次数: 0

Loss of Prominin 2 expression inhibits AKT/mTOR signaling to limit glycolysis and drive ferroptosis in breast cancer cells 在乳腺癌细胞中，pronin2表达缺失可抑制AKT/mTOR信号通路限制糖酵解并驱动铁下垂。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-14 DOI: 10.1016/j.bbamcr.2025.120047

Lei Yin , Yanze Lin , Zhongdian Yuan , Rexiati Ruze , Zhen Yang , Yingmei Shao

{"title":"Loss of Prominin 2 expression inhibits AKT/mTOR signaling to limit glycolysis and drive ferroptosis in breast cancer cells","authors":"Lei Yin , Yanze Lin , Zhongdian Yuan , Rexiati Ruze , Zhen Yang , Yingmei Shao","doi":"10.1016/j.bbamcr.2025.120047","DOIUrl":"10.1016/j.bbamcr.2025.120047","url":null,"abstract":"<div><div>This study aimed to characterize the oncogenic functions of Prominin 2 (<em>PROM2</em>), the pro-cancer and ferroptosis resistance gene, in breast cancer (BC). <em>PROM2</em> expression was analyzed using single-cell RNA sequencing and the TCGA database. Its expression was confirmed in BC tissues and cell lines using qRT-PCR, immunohistochemistry, and western blot assays. The effects of <em>PROM2</em> were evaluated <em>in vivo</em> and <em>in vitro</em>. RNA sequencing and GSEA were used to investigate the potential underlying molecular mechanisms of <em>PROM2</em> in BC. Co-immunoprecipitation was used to determine the interaction between AKT and PROM2. <em>PROM2</em> expression was elevated in clinical samples and BC cells and positively correlated with a worse prognosis. Functional experiments demonstrated that <em>PROM2</em> silencing suppressed tumor growth and malignancy. Mechanistically, PROM2 interacts with AKT to activate mTOR signaling, thereby promoting glycolysis and inhibiting ferroptosis. Specifically, for glycolysis, <em>PROM2</em> silencing decreased glucose uptake, extracellular acidification rate, lactate production, and glycolysis-related enzyme expression, while increasing oxygen consumption. For ferroptosis, <em>PROM2</em> silencing upregulated reactive oxygen species, malondialdehyde, iron, Fe<sup>2+</sup>, and downregulated SLC7A11, GPX4, and glutathione levels. Overexpression of AKT or the AKT agonist (SC79) reversed the effects of <em>PROM2</em> silencing on BC cell glycolysis and ferroptosis. Our results suggest that <em>PROM2</em> is an oncogenic gene that supports BC progression by enhancing glycolysis and inhibiting ferroptosis <em>via</em> AKT/mTOR signaling. Therefore, <em>PROM2</em> may be a potential therapeutic target for BC treatment.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120047"},"PeriodicalIF":3.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862092","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}

引用次数: 0

ESCO2 drives breast cancer proliferation and metastasis through PI3K/AKT/mTOR phosphorylation: A potential therapeutic target ESCO2通过PI3K/AKT/mTOR磷酸化驱动乳腺癌增殖和转移：一个潜在的治疗靶点

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-10 DOI: 10.1016/j.bbamcr.2025.120043

Pingchuan Li , Lineng Wei , Meng Li , Huawei Yang

{"title":"ESCO2 drives breast cancer proliferation and metastasis through PI3K/AKT/mTOR phosphorylation: A potential therapeutic target","authors":"Pingchuan Li , Lineng Wei , Meng Li , Huawei Yang","doi":"10.1016/j.bbamcr.2025.120043","DOIUrl":"10.1016/j.bbamcr.2025.120043","url":null,"abstract":"<div><div>Breast cancer remains a major global health threat to women, underscoring the urgent need for novel therapeutic targets. While ESCO2, an essential cell cycle regulator, has been implicated in cancer progression, its precise role and molecular mechanisms in breast cancer remain poorly understood. In this study, we first demonstrated significant upregulation of ESCO2 in breast cancer through analysis of TCGA and GEO datasets, which was further validated in clinical specimens and cell lines, with its expression correlating with advanced T-stage, aggressive molecular subtypes and poor prognosis. Functional studies in MDA-MB-231 and MDA-MB-468 cells revealed that ESCO2 overexpression promoted cell proliferation, migration and invasion, while its knockdown exerted opposite effects. Mechanistic investigations uncovered that ESCO2 depletion reduced phosphorylation of PI3K/AKT/mTOR pathway components, and co-immunoprecipitation assays confirmed direct interaction between ESCO2 and PI3K. Importantly, the tumor-suppressive effects of ESCO2 knockdown could be rescued by SC79-mediated AKT activation. In vivo experiments using xenograft mouse models consistently showed that ESCO2 silencing significantly inhibited tumor growth, increased apoptosis and necrosis, and reduced metastasis. Collectively, our findings establish ESCO2 as a novel oncogene driving breast cancer progression through PI3K/AKT/mTOR pathway activation, highlighting its potential as a promising therapeutic target for breast cancer intervention.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120043"},"PeriodicalIF":3.7,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833875","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}

引用次数: 0

Prolyl isomerase Pin4 impacts estrogen receptor transactivation by enhancing phosphorylation and consequently promotes the proliferation of breast cancer cells 脯氨酸异构酶Pin4通过增强磷酸化影响雌激素受体的反活化，从而促进乳腺癌细胞的增殖。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-10 DOI: 10.1016/j.bbamcr.2025.120044

Masa-Ki Inoue , Rena Ueda , Mikako Nakanishi , Machi Kanna , Yasuka Matsunaga , Tomoichiro Asano , Yusuke Nakatsu

{"title":"Prolyl isomerase Pin4 impacts estrogen receptor transactivation by enhancing phosphorylation and consequently promotes the proliferation of breast cancer cells","authors":"Masa-Ki Inoue , Rena Ueda , Mikako Nakanishi , Machi Kanna , Yasuka Matsunaga , Tomoichiro Asano , Yusuke Nakatsu","doi":"10.1016/j.bbamcr.2025.120044","DOIUrl":"10.1016/j.bbamcr.2025.120044","url":null,"abstract":"<div><div>Breast cancer is the most common tumor in women, and approximately 70 % of cases are diagnosed to be estrogen receptor α (ERα)-positive. Estradiol (E2)-ERα signaling is undoubtedly involved in the development of breast cancer, and the upregulation of this pathway is linked to tamoxifen resistance. However, ERα regulation is complex, and the underlying mechanisms have not been comprehensively elucidated.</div><div>Pin4 is a prolyl isomerase that promotes cis-trans isomerization of proline residues. Although its role remains unclear, an analysis of public databases reveals that Pin4 expression in breast cancer tissues is higher than that in normal tissues.</div><div>Here, we reveal that Pin4 regulates ERα transcriptional activity and is essential for the proliferation of ERα-positive breast cancer cells. In MCF7 and T47D cells, Pin4 knockdown drastically decreased cell proliferation by inducing cell cycle arrest. In addition, the silencing of Pin4 impaired the expression of E2-induced genes, including E2F1. We also found that Pin4 interacted with ERα and affected its transcriptional activity by promoting phosphorylation at Ser167, which was involved in the recruitment of steroid receptor coactivator-3 (SRC-3) into ERα. Importantly, the silence of Pin4 gene in T47D cells attenuated the interaction between SRC-3 and ERα.</div><div>Collectively, the study findings show that Pin4 is a critical factor in the development of ERα-positive breast cancers and the identification of Pin4 inhibitors could be a promising therapeutic strategy.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120044"},"PeriodicalIF":3.7,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833887","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}

引用次数: 0

Hyperosmolarity-induced activation of PIEZO1 engages detrimental calcium/oxidative stress signaling and adaptive catalase response in renal inner medullary collecting duct (mIMCD3) cells 高渗透压诱导的PIEZO1激活在肾髓内收集管（mIMCD3）细胞中参与有害的钙/氧化应激信号和适应性过氧化氢酶反应。

IF 3.7 2区生物学

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-08-07 DOI: 10.1016/j.bbamcr.2025.120041

Stephanie Probst , Nadiya Romanova , Robin Herbrechter , Teresa Kern , Marie Bergmeier , Wing-Kee Lee , Frank Thévenod

{"title":"Hyperosmolarity-induced activation of PIEZO1 engages detrimental calcium/oxidative stress signaling and adaptive catalase response in renal inner medullary collecting duct (mIMCD3) cells","authors":"Stephanie Probst , Nadiya Romanova , Robin Herbrechter , Teresa Kern , Marie Bergmeier , Wing-Kee Lee , Frank Thévenod","doi":"10.1016/j.bbamcr.2025.120041","DOIUrl":"10.1016/j.bbamcr.2025.120041","url":null,"abstract":"<div><div>The collecting duct (CD) is the final segment of the renal nephron and is involved in the fine regulation of osmotic and ionic homeostasis. Its medullary segment is continuously exposed to a wide spectrum of osmotic gradients and resultant osmotic stress. Strikingly, the expression of the mechanically activated non-selective cationic and Ca<sup>2+</sup>-permeable transduction ion channel PIEZO1 is most prominent in inner medullary CD (IMCD) cells, yet its functions there are still not well understood. We hypothesized increased PIEZO1 expression in the IMCD could be linked to its hyperosmotic stress environment. Using the mouse mIMCD<sub>3</sub> cell line, which has been used to characterize hyperosmotic stress-induced cell death, we demonstrate twice as much PIEZO1 expression compared to proximal tubule (WKPT-0293 Cl.2) or cortical CD (mCCD(cl.1)) cell lines. Hyperosmolarity/−tonicity by addition of NaCl ± urea to the culture medium (+ 100–300 mosmol/l) or PIEZO1 agonist Yoda1 (20 μmol/l) decreased mIMCD<sub>3</sub> cell viability assayed by MTT, which were antagonized by PIEZO1 inhibitors GsMTx4 (2.5 μmol/l) and salvianolic acid (SalB, 10 μmol/l). PIEZO1 activation by hyperosmolarity and agonists (Yoda1, Jedi1) increased Ca<sup>2+</sup> influx, downstream reactive oxygen species (ROS), in particular mitochondrial superoxide (O<sub>2</sub><sup>•-</sup>) formation, and subsequent adaptive ROS-decomposing catalase expression and activity that were sensitive to PIEZO1 antagonists (GsMTx4, SalB). Hence, the data demonstrate hyperosmolarity/−tonicity of the kidney elicits PIEZO1 activation, mitochondrial ROS formation and cell death that are partially countered by catalase-mediated stress adaptation.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 8","pages":"Article 120041"},"PeriodicalIF":3.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803337","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}

引用次数: 0