Journal of Molecular Cell Biology最新文献

Novel roles of ammonia in physiology and cancer.

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-03-06 DOI: 10.1093/jmcb/mjaf007

Guantong Chen, Chenxi Wang, Shuo Huang, Shibo Yang, Qiyuan Su, Yige Wang, Weiwei Dai

{"title":"Novel roles of ammonia in physiology and cancer.","authors":"Guantong Chen, Chenxi Wang, Shuo Huang, Shibo Yang, Qiyuan Su, Yige Wang, Weiwei Dai","doi":"10.1093/jmcb/mjaf007","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf007","url":null,"abstract":"Ammonia, traditionally recognized as a toxic nitrogen waste product, has recently emerged as a significant player in diverse physiological processes and implicated in cancer biology. This review article provides an overview of the multifaceted impact of ammonia on cellular signaling pathways, energy metabolism, and tumor microenvironment dynamics, in particular its novel roles in neurotransmission, metabolic homeostasis, cancer cell proliferation, and immune modulation. Notably, ammonia accumulates within the tumor microenvironment, promoting non-essential amino acid synthesis, stimulating mTORC1 activation, promoting lipid synthesis, and impairing various immune cell functions, thereby promoting tumor progression. Furthermore, the potential dual role of ammonia as tumorigenic factor and cancer therapeutic target are discussed, shedding light on its complex regulatory mechanisms and clinical implications. This timely review aims to deepen our understanding of the emerging physiological and pathological roles of ammonia, offering valuable insights into its significance as a potential target for diagnostic and therapeutic interventions in cancer and beyond.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573275","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

Combination Therapy Dramatically Promotes Remyelination.

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-02-28 DOI: 10.1093/jmcb/mjaf005

Yawen Li, Pingping Li, Yixuan Song, Wenjun Zhang, Xinyue Jiang, Siyi Chen, Wei Luo, Caiyun Ma, Changqing Liu, Jianguo Niu, Aibin Liang, Yarui Du, Bo O Zhou, Mingliang Zhang

{"title":"Combination Therapy Dramatically Promotes Remyelination.","authors":"Yawen Li, Pingping Li, Yixuan Song, Wenjun Zhang, Xinyue Jiang, Siyi Chen, Wei Luo, Caiyun Ma, Changqing Liu, Jianguo Niu, Aibin Liang, Yarui Du, Bo O Zhou, Mingliang Zhang","doi":"10.1093/jmcb/mjaf005","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf005","url":null,"abstract":"Multiple sclerosis (MS) is an immune-mediated disease in the central nervous system that is characterized by demyelination, axonal degeneration, and progressive neurological disability and is so far incurable. Current medications are predominantly immune-targeted but fail to prevent disease progression due to their inability to actively promote remyelination. Small molecules have been reported to promote myelin regeneration but their therapeutic efficacy is limited by insufficient immune modulation. Thus, the strategies achieving both immunomodulation and active myelin regeneration are highly desired. Here, we investigated a combination therapy (CT) for MS designed to simultaneously modulate immune responses and promote oligodendrocyte precursor cell (OPC) differentiation and in situ remyelination in an experimental autoimmune encephalomyelitis (EAE) mouse model. Remarkably, CT suppressed acute inflammatory activity, activated the signaling pathways for myelin development, induced the expression of myelin-related genes, and significantly promoted remyelination and the recovery of motor performance. Furthermore, a reduced immunomodulator dosage or shorter treatment duration with small-molecule drugs achieved comparable symptom reversal. Our findings demonstrate the potential of CT to address complex pathobiology and lay a foundation for developing novel therapeutic strategies for MS.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557192","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

Argon improves microglia-mediated hippocampal neuronal hyperexcitability to alleviate anxiety-like behaviors in mice.

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-02-28 DOI: 10.1093/jmcb/mjaf006

Jie Cheng, Baiyang Zheng, Shusu Luo, Yuan Yuan, Xiaobo Wu, Zhenglin Jiang, Xia Li

{"title":"Argon improves microglia-mediated hippocampal neuronal hyperexcitability to alleviate anxiety-like behaviors in mice.","authors":"Jie Cheng, Baiyang Zheng, Shusu Luo, Yuan Yuan, Xiaobo Wu, Zhenglin Jiang, Xia Li","doi":"10.1093/jmcb/mjaf006","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf006","url":null,"abstract":"The role of inflammation in psychiatric disorders, such as anxiety, has gained increasing attention, with the hippocampus being identified as a key region involved in emotional regulation. Argon has been reported to alleviate the symptoms of psychiatric disorders; however, its underlying mechanism remains unclear. In this study, we found that argon significantly suppressed lipopolysaccharide (LPS)-induced anxiety-like behaviors and attenuated hippocampal neuronal hyperexcitability in mice. By analyzing neuronal excitability following microglial depletion and subsequent repopulation, as well as assessing microglial morphology, we confirmed that microglia are key targets of inflammation and validated the inhibitory effects of argon. Electrophysiological studies and transcriptome sequencing revealed that argon inhibited the microglia-released inflammatory cytokines via the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway, thereby improving the excitability of hippocampal neurons. Collectively, this study provides evidence that the regulation of microglia may be the underlying mechanism by which argon ameliorates neuroinflammation-induced anxiety-like behaviors.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557190","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

Comments on 'Vimentin intermediate filaments coordinate actin stress fibers and podosomes to determine the extracellular matrix degradation by macrophages'.

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-02-27 DOI: 10.1093/jmcb/mjaf004

Sandrine Etienne-Manneville

引用次数: 0

Multivalent interactions of Septin 6 promote the establishment of epithelial cell polarity.

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-02-19 DOI: 10.1093/jmcb/mjaf003

Weihong Fu, Xueying Wang, Mussarat Rafiq, Hengyi Shao, Cunyu Wang, Dongmei Wang, Changlu Tao, Chuanhai Fu, Barbara Zieger, Xing Liu, Xuebiao Yao, Liangyu Zhang

{"title":"Multivalent interactions of Septin 6 promote the establishment of epithelial cell polarity.","authors":"Weihong Fu, Xueying Wang, Mussarat Rafiq, Hengyi Shao, Cunyu Wang, Dongmei Wang, Changlu Tao, Chuanhai Fu, Barbara Zieger, Xing Liu, Xuebiao Yao, Liangyu Zhang","doi":"10.1093/jmcb/mjaf003","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf003","url":null,"abstract":"Septins, components of the fourth cytoskeleton, play an indispensable role in establishing and maintaining epithelial cell polarity. However, the molecular mechanisms underlying the dynamic assembly of higher-order septin structures and the establishment of epithelial cell polarity remain elusive. Here, we show that septins form a previously unrecognized dynamic structure with liquid-like properties in polarized MDCK cells. We identified Septin 6 (SEPT6) as the key human septin that undergoes liquid-liquid phase separation (LLPS) both in vitro and in vivo through weak, multivalent interactions mediated by its C-terminal tail. SEPT6 mutants defective in LLPS in vitro also fail to support adherens junction integrity and cell polarity establishment in 2D and 3D cell cultures. Our findings indicate that weak, multivalent interactions are essential for the assembly of higher-order septin structures in cells. We propose that these interactions, in conjunction with conventional interactions between folded domains, generate partially ordered septin assemblies that support the apical-basal axis and lumen formation in metazoans.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457561","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

ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism.

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-02-06 DOI: 10.1093/jmcb/mjaf001

Zhikun Li, Kaixiang Fan, Caixia Suo, Xuemei Gu, Chuxu Zhu, Haoran Wei, Liang Chen, Ping Gao, Linchong Sun

{"title":"ENO1-BACE2-mediated LDLR cleavage promotes liver cancer progression by remodelling cholesterol metabolism.","authors":"Zhikun Li, Kaixiang Fan, Caixia Suo, Xuemei Gu, Chuxu Zhu, Haoran Wei, Liang Chen, Ping Gao, Linchong Sun","doi":"10.1093/jmcb/mjaf001","DOIUrl":"https://doi.org/10.1093/jmcb/mjaf001","url":null,"abstract":"Enolase 1 (ENO1) is a glycolytic enzyme involved in tumour progression that performs a variety of classical and nonclassical functions. However, the mechanism by which it promotes tumour progression is still not fully understood. Here, we found that ENO1 can bind to β-site amyloid precursor protein cleaving enzyme 2 (BACE2), a codependent gene of ENO1, in liver cancer cells. By suppressing lysosomal-dependent degradation, ENO1 stabilises BACE2 protein level without affecting its mRNA level. Further analysis revealed that ENO1 and BACE2 promote low-density lipoprotein receptor (LDLR) cleavage, leading to decreased absorption of exogenous cholesterol. To maintain intracellular cholesterol levels, ENO1 and BACE2 upregulate the expression of genes involved in de novo cholesterol synthesis through a negative feedback mechanism. Both in vitro and in vivo, BACE2 mediates the tumour-promoting effect of ENO1 in liver cancer. Finally, high expression levels of ENO1 and BACE2 and low expression levels of LDLR were detected in clinical HCC samples, and abnormal expression of the ENO1-BACE2-LDLR axis was significantly associated with poor prognosis in patients with liver cancer. These data collectively demonstrated that ENO1 functions in protein cleavage by binding to BACE2 and promotes liver cancer progression by reprogramming cholesterol metabolism.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365117","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

A polarized multicomponent foundation upholds ciliary central microtubules. 纤毛中心微管由极化的多成分基础支撑。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-01-30 DOI: 10.1093/jmcb/mjae031

Qingxia Chen, Huijie Zhao, Xinwen Pan, Chuyu Fang, Benhua Qiu, Jingting Guo, Xiumin Yan, Xueliang Zhu

{"title":"A polarized multicomponent foundation upholds ciliary central microtubules.","authors":"Qingxia Chen, Huijie Zhao, Xinwen Pan, Chuyu Fang, Benhua Qiu, Jingting Guo, Xiumin Yan, Xueliang Zhu","doi":"10.1093/jmcb/mjae031","DOIUrl":"10.1093/jmcb/mjae031","url":null,"abstract":"Cilia's back-and-forth beat pattern requires a central pair (CP) of microtubules. However, the mechanism by which the CP is upheld above the transition zone (TZ) remains unclear. Here, we showed that a rod-like substructure marked by Cep131 and ciliary Centrin serves as a polarized CP-supporting foundation. This CP-foundation (CPF) was assembled independently of the CP during ciliogenesis in mouse ependymal cells. It protruded from the distal end of the basal body out of the TZ to enwrap the proximal end of the CP. Through proximity labeling, we identified 26 potential CPF components, among which Ccdc148 specifically localized at the proximal region of Centrin-decorated CPF and was complementary to the Cep131-enriched distal region. Cep131 deficiency abolished the CPF, resulting in CP penetration into the TZ. Consequently, cilia became prone to ultrastructural abnormality and paralysis, and Cep131-deficient mice were susceptible to late-onset hydrocephalus. In addition to Centrin, phylogenetic analysis also indicated conservations of Ccdc131 and Ccdc148 from protists to mammals, suggesting that the CPF is an evolutionarily conserved multicomponent CP-supporting platform in cilia.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010230","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}

引用次数: 0

Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression. Temsirolimus 可抑制 FSP1 酶的活性，从而诱导铁变态反应，抑制肝癌的进展。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-01-30 DOI: 10.1093/jmcb/mjae036

Rui-Lin Tian, Tian-Xiang Wang, Zi-Xuan Huang, Zhen Yang, Kun-Liang Guan, Yue Xiong, Pu Wang, Dan Ye

{"title":"Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression.","authors":"Rui-Lin Tian, Tian-Xiang Wang, Zi-Xuan Huang, Zhen Yang, Kun-Liang Guan, Yue Xiong, Pu Wang, Dan Ye","doi":"10.1093/jmcb/mjae036","DOIUrl":"10.1093/jmcb/mjae036","url":null,"abstract":"Ferroptosis is a non-apoptotic mode of cell death characterized by iron-dependent accumulation of lipid peroxidation. While lipid radical elimination reaction catalyzed by glutathione peroxidase 4 (GPX4) is a major anti-ferroptosis mechanism, inhibiting this pathway pharmaceutically shows promise as an antitumor strategy. However, certain tumor cells exhibit redundancy in lipid radical elimination pathways, rendering them unresponsive to GPX4 inhibitors. In this study, we conducted screens across different cancer cell lines and Food and Drug Administration-approved drugs, leading to the identification of temsirolimus in combination with the GPX4 inhibitor RSL3 as a potent inducer of ferroptosis in liver cancer cells. Mechanistically, temsirolimus sensitized liver cancer cells to ferroptosis by directly binding to and inhibiting ferroptosis suppressor protein 1 (FSP1) enzyme. Notably, while temsirolimus is recognized as a potent mammalian target of rapamycin (mTOR) inhibitor, its ferroptosis-inducing effect is primarily attributed to the inhibition of FSP1 rather than mTOR activity. By employing in vitro colony formation assays and in vivo tumor xenograft models, we demonstrated that the combination of temsirolimus and RSL3 effectively suppressed liver tumor progression. This tumoricidal effect was associated with increased lipid peroxidation and induction of ferroptosis. In conclusion, our findings underscore the potential of combining multitarget ferroptosis-inducing agents to circumvent the resistance to ferroptosis of liver cancer cells and highlight temsirolimus as a promising FSP1 inhibitor and ferroptosis inducer, which also deserves further investigation in translational medicine.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307934","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}

引用次数: 0

Correction to: Mitochondrial aldehyde dehydrogenase rescues against diabetic cardiomyopathy through GSK3β-mediated preservation of mitochondrial integrity and Parkin-mediated mitophagy. 更正为线粒体醛脱氢酶通过 GSK3β 介导的线粒体完整性保护和 Parkin 介导的有丝分裂，拯救糖尿病心肌病。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-01-30 DOI: 10.1093/jmcb/mjae032

引用次数: 0

ATP promotes protein coacervation through conformational compaction. ATP 通过构象压实促进蛋白质共轭。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2025-01-30 DOI: 10.1093/jmcb/mjae038

Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong

{"title":"ATP promotes protein coacervation through conformational compaction.","authors":"Yueling Zhu, Shiyan Lin, Lingshen Meng, Min Sun, Maili Liu, Jingyuan Li, Chun Tang, Zhou Gong","doi":"10.1093/jmcb/mjae038","DOIUrl":"10.1093/jmcb/mjae038","url":null,"abstract":"Adenosine triphosphate (ATP) has been recognized as a hydrotrope in the phase separation process of intrinsically disordered proteins (IDPs). Surprisingly, when using the disordered Arg-Gly/Arg-Gly-Gly (RG/RGG) rich motif from the HNRNPG protein as a model system, we discover a biphasic relationship between the ATP concentration and IDP phase separation. We show that, at a relatively low ATP concentration, ATP dynamically interacts with the IDP, which neutralizes protein surface charges, promotes intermolecular interactions, and consequently promotes phase separation. We further demonstrate that ATP induces a compact conformation of the IDP, accounting for the reduced solvent exchange rate and lower compression ratio during phase separation. As ATP concentration increases, its hydrotropic properties emerge, leading to the dissolution of the phase-separated droplets. Our finding uncovers a complex mechanism by which ATP molecules modulate the structure, interaction, and phase separation of IDPs and accounts for the distinct phase separation behaviors of the charge-rich RGG motif and other low-complexity IDPs.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361585","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}

引用次数: 0