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Unraveling Mycobacterium tuberculosis acid resistance and pH homeostasis mechanisms.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-24 DOI: 10.1002/1873-3468.70023
Janïs Laudouze, Stéphane Canaan, Alexandre Gouzy, Pierre Santucci
{"title":"Unraveling Mycobacterium tuberculosis acid resistance and pH homeostasis mechanisms.","authors":"Janïs Laudouze, Stéphane Canaan, Alexandre Gouzy, Pierre Santucci","doi":"10.1002/1873-3468.70023","DOIUrl":"https://doi.org/10.1002/1873-3468.70023","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (Mtb) is a successful pathogen that has developed a variety of strategies to survive and replicate within host cells. Among them, resistance mechanisms that allow Mtb to cope with the acidic environment of the endolysosomal network play a crucial role in its host adaptation and pathogenesis. In this Review, we summarize our understanding regarding the molecular factors contributing to Mtb acid resistance and the maintenance of intrabacterial pH homeostasis within in vitro and in cellulo systems. We also discuss some of the recently emerged concepts regarding host adaptation to acid stress, with a special emphasis on central carbon metabolism. Finally, we introduce some of the current and future direction(s) in this fast-evolving field of research.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Acute oxygen sensing by arterial chemoreceptors with a mutant mitochondrial complex I ND6 subunit lacking reverse electron transport.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-21 DOI: 10.1002/1873-3468.70017
María Torres-López, Pedro F Spiller, Lin Gao, Paula García-Flores, Michael P Murphy, Patricia Ortega-Sáenz, José López-Barneo
{"title":"Acute oxygen sensing by arterial chemoreceptors with a mutant mitochondrial complex I ND6 subunit lacking reverse electron transport.","authors":"María Torres-López, Pedro F Spiller, Lin Gao, Paula García-Flores, Michael P Murphy, Patricia Ortega-Sáenz, José López-Barneo","doi":"10.1002/1873-3468.70017","DOIUrl":"https://doi.org/10.1002/1873-3468.70017","url":null,"abstract":"<p><p>Carotid body glomus cells are essential for stimulating breathing in response to hypoxia. They contain specialized mitochondria in which hypoxia induces the accumulation of NADH and H<sub>2</sub>O<sub>2</sub> that modulate membrane ion channel activity. We investigated whether hypoxia induces reverse electron transport (RET) at mitochondrial complex I (MCI). We studied glomus cells from mice with a mutation in ND6, a core protein of MCI, which maintain normal MCI NADH dehydrogenase activity but cannot catalyze RET. The ND6 mutation increases the propensity of MCI to deactivate, and glomus cells with deactivated MCI are insensitive to acute hypoxia. These findings further indicate that MCI function is necessary for glomus cell responsiveness to hypoxia, although MCI RET does not seem to be required for this process.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Structural differences in the outer membrane-associated flagellar rings between sheathed and unsheathed flagella.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-20 DOI: 10.1002/1873-3468.70011
Przemysław Dutka, Ethan H Li, Tengfei Zhong, Grant J Jensen, Mohammed Kaplan
{"title":"Structural differences in the outer membrane-associated flagellar rings between sheathed and unsheathed flagella.","authors":"Przemysław Dutka, Ethan H Li, Tengfei Zhong, Grant J Jensen, Mohammed Kaplan","doi":"10.1002/1873-3468.70011","DOIUrl":"https://doi.org/10.1002/1873-3468.70011","url":null,"abstract":"<p><p>The bacterial flagellar motor generates a torque to move the bacterium in its environment. Despite sharing a conserved core, flagellar motors of different species exhibit structural diversity with species-specific embellishments. These embellishments are classified into various types, including integrated (spanning the whole periplasmic space) or outer membrane (OM)-associated ones. Here, we used cryo-electron tomography to investigate the structural differences between the embellishments of sheathed and unsheathed flagella in various species. We discovered that the integrated embellishments of sheathed flagella have disks and rings with a constant diameter, while those of unsheathed flagella have components that vary significantly in diameter. Both unsheathed and sheathed flagella with OM-associated embellishments have components with constant diameter with a subset of motors having an additional extracellular ring. In this Hypothesis article, we propose that these differences may play a role in the formation of the sheath, as having large protein disks of various diameters underneath the OM may interfere with membrane bending to form the sheath.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Structural insights into the Shigella flexneri GmvAT toxin-antitoxin system.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-20 DOI: 10.1002/1873-3468.70015
Ran Chen, Hui Zhao, Jie Zhou, Aoyun Liu, Yinfeng Guo, Kejue Wu, Yongle Xiang, Jinping Lei, Songshan Jiang, Wei Xie
{"title":"Structural insights into the Shigella flexneri GmvAT toxin-antitoxin system.","authors":"Ran Chen, Hui Zhao, Jie Zhou, Aoyun Liu, Yinfeng Guo, Kejue Wu, Yongle Xiang, Jinping Lei, Songshan Jiang, Wei Xie","doi":"10.1002/1873-3468.70015","DOIUrl":"https://doi.org/10.1002/1873-3468.70015","url":null,"abstract":"<p><p>Toxin-antitoxin (TA) systems are common bicistronic gene elements in bacteria and are critical for stress responses. The toxin members of the GNAT/RHH TA family can acetylate certain aminoacylated tRNA molecules and inhibit global protein translation. One member named GmvT is important for virulence plasmid maintenance in Shigella flexneri, but the underlying mechanism remains poorly understood. Here, we report the cocrystal structures of GmvT in two forms. The binding of the antitoxin mainly relies on the backbone of the toxin while the cofactor is free of contacts with the antitoxin, supported by follow-up in vitro and in vivo studies. Our study provides insight into the protein-protein/protein-ligand interactions of the GmvAT pair and the structural basis for molecular recognition.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Clathrin functions in intracellular sorting during receptor-mediated endocytosis.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-20 DOI: 10.1002/1873-3468.70016
Mai Itagaki, Noriyasu Kamei
{"title":"Clathrin functions in intracellular sorting during receptor-mediated endocytosis.","authors":"Mai Itagaki, Noriyasu Kamei","doi":"10.1002/1873-3468.70016","DOIUrl":"https://doi.org/10.1002/1873-3468.70016","url":null,"abstract":"<p><p>Clathrin is a key protein involved in receptor-mediated endocytosis (RME), which is also known as clathrin-mediated endocytosis (CME). Ligand/receptor binding facilitates clathrin clustering and cell surface invagination. We recently found that the typical CME ligand transferrin (Tf) can be internalized into cells without the clathrin heavy chain (CLTC). In this study, we clarified the unknown roles of clathrin during intracellular trafficking. Microscopic observation revealed that Tf accumulates in the deeper compartments of CLTC-knockdown HeLa cells. A colocalization analysis with endosome/lysosome markers showed that endocytosed Tf moves to early/late endosomes and then to lysosomes in CLTC-knockdown cells. This suggests that clathrin contributes to the recycling and exocytosis of endocytosed molecules.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Immunoregulatory mechanisms of the arachidonic acid pathway in cancer.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-20 DOI: 10.1002/1873-3468.70013
Maria Tredicine, Matteo Mucci, Antonio Recchiuti, Domenico Mattoscio
{"title":"Immunoregulatory mechanisms of the arachidonic acid pathway in cancer.","authors":"Maria Tredicine, Matteo Mucci, Antonio Recchiuti, Domenico Mattoscio","doi":"10.1002/1873-3468.70013","DOIUrl":"https://doi.org/10.1002/1873-3468.70013","url":null,"abstract":"<p><p>The arachidonic acid (AA) pathway promotes tumor progression by modulating the complex interactions between cancer and immune cells within the microenvironment. In this Review, we summarize the knowledge acquired thus far concerning the intricate mechanisms through which eicosanoids either promote or suppress the antitumor immune response. In addition, we will discuss the impact of eicosanoids on immune cells and how they affect responsiveness to immunotherapy, as well as potential strategies for manipulating the AA pathway to improve anticancer immunotherapy. Understanding the molecular pathways and mechanisms underlying the role played by AA and its metabolites in tumor progression may contribute to the development of more effective anticancer immunotherapies.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Distinct dysregulated pathways in sporadic and Lynch syndrome-associated colorectal cancer offer insights for targeted treatment.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-20 DOI: 10.1002/1873-3468.70010
May J Krause, Musalula Sinkala, Raj Ramesar
{"title":"Distinct dysregulated pathways in sporadic and Lynch syndrome-associated colorectal cancer offer insights for targeted treatment.","authors":"May J Krause, Musalula Sinkala, Raj Ramesar","doi":"10.1002/1873-3468.70010","DOIUrl":"https://doi.org/10.1002/1873-3468.70010","url":null,"abstract":"<p><p>Lynch syndrome (LS) is a hereditary disorder that increases the risk of colorectal cancer (CRC) due to constitutional pathogenic variants in mismatch repair (MMR) genes. When coupled with somatic mutations in the same gene, MMR deficiency occurs. However, the mechanisms driving cancer development remain unclear. This study aimed to identify distinct molecular drivers in LS-associated and sporadic CRC. We found that PI3K-Akt signalling is dysregulated in LS-associated CRC, while Wnt signalling predominates in sporadic CRC. Moreover, our findings highlight the therapeutic potential of PI3K-Akt pathway inhibitors, such as taselisib, for LS-associated CRC patients with high pathway dependency. Similarly, Wnt signalling pathway inhibitors, such as XAV939, offer a promising therapeutic approach for sporadic CRC. These findings underscore the importance of understanding the biological basis of disease for developing targeted therapies tailored to CRC subtype-specific oncogenic pathways.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Identification of a basal body-localized epsilon-tubulin in Leishmania. 鉴定利什曼原虫基底体定位的epsilon-tubulin。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-19 DOI: 10.1002/1873-3468.70012
Arunava Seth, Anubhab Das, Rupak Datta
{"title":"Identification of a basal body-localized epsilon-tubulin in Leishmania.","authors":"Arunava Seth, Anubhab Das, Rupak Datta","doi":"10.1002/1873-3468.70012","DOIUrl":"https://doi.org/10.1002/1873-3468.70012","url":null,"abstract":"<p><p>Epsilon-tubulins have been identified in only a few organisms to date. We identified an epsilon-tubulin in Leishmania major (Lmε-tubulin) exhibiting significant sequence similarity and conservation of functional domains with its counterparts. It is expressed in both promastigote and amastigote forms of the parasite. For localization studies, we generated a Leishmania strain expressing the endogenous Lmε-tubulin tagged with mNeonGreen by CRISPR-Cas9. Imaging of this strain revealed that Lmε-tubulin is located near the kinetoplast and at the flagellar base, indicating basal body localization. Lmε-tubulin is not part of the microtubular network since its localization remained unaltered upon treatment with nocodazole, a microtubule disruptor. This is the first experimental identification of an ε-tubulin not only in Leishmania but in the entire Trypanosomatidae family.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The enigmatic world of tear extracellular vesicles (EVs)-exploring their role in ocular health and beyond.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-17 DOI: 10.1002/1873-3468.70004
Azima Fatima, Shalini Sanyal, Gaurab Kumar Jha, Swathi Kaliki, Rani Pallavi
{"title":"The enigmatic world of tear extracellular vesicles (EVs)-exploring their role in ocular health and beyond.","authors":"Azima Fatima, Shalini Sanyal, Gaurab Kumar Jha, Swathi Kaliki, Rani Pallavi","doi":"10.1002/1873-3468.70004","DOIUrl":"https://doi.org/10.1002/1873-3468.70004","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are released by all kind of cells into the extracellular space, where they shuttle parental cell-derived molecular cargoes (DNA, RNA, proteins) to both adjacent and distant cells, influencing the physiology of target cells. Their specific cargo content and abundance in liquid biopsies make them excellent candidates for biomarker studies. Indeed, EVs isolated from various body fluids, including blood, pleural fluid, urine, cerebrospinal fluid, saliva, milk, ascites, and tears, have been recognized for their potential as biomarkers in diagnosis, monitoring treatment, and predicting outcomes for various diseases. Increasing studies suggest that tears have great promise as a noninvasive liquid biopsy source for EVs. Our aim here is to provide a comprehensive review of the exploration of tears as a noninvasive reservoir of EVs and their contents, evaluating their accessibility and potential utility as a liquid biopsy method. Additionally, the potential of tear EVs in various cancers, including ocular cancer, is discussed. Finally, the advantages and challenges of employing tear-based liquid biopsy for EVs for the disease's biomarker studies are evaluated.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Brain lipidomic profiles of sleep enhancement through co-administration of alprazolam and CGS21680.
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-17 DOI: 10.1002/1873-3468.70009
Yi Zhang, Xingle Xia, Qian Jin, Guixiang Yang, Manzhu Cao, Xingxing Zong, Jingjing Shi, Chen Wang, Liqin Li
{"title":"Brain lipidomic profiles of sleep enhancement through co-administration of alprazolam and CGS21680.","authors":"Yi Zhang, Xingle Xia, Qian Jin, Guixiang Yang, Manzhu Cao, Xingxing Zong, Jingjing Shi, Chen Wang, Liqin Li","doi":"10.1002/1873-3468.70009","DOIUrl":"https://doi.org/10.1002/1873-3468.70009","url":null,"abstract":"<p><p>Alprazolam and CGS21680 are both drugs known for their sleep and sedation effects. The study aimed to utilize mass spectrometry imaging to assess the regulatory changes in brain lipids of mice by the sleep-enhancing effects of the co-administration of alprazolam and CGS21680. A seven-day continuous administration mouse model was established using alprazolam and CGS21680. Glycerophosphoinositols were elevated in nine regions, glycerophosphoglycerols rising in six brain regions, and glycerophosphoserines increasing in six regions. Other lipid classes exhibited reductions, with fatty acids decreasing in 10 regions, carnitines in seven regions, ceramides in nine regions, and diacylglycerols in 10 regions. The research provides valuable insights into sleep-related regulation pathways by delineating the regulation of various lipid biomarkers in multiple brain regions.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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