Cell reports最新文献_第9页

Prefrontal ErbB4-positive interneurons for avoidance. 前额叶erbb4阳性中间神经元。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-29 DOI: 10.1016/j.celrep.2025.115628

Wanpeng Cui, Chen Shen, Wen-Cheng Xiong, Lin Mei

引用次数: 0

Activity-dependent degradation of Kv4.2 contributes to synaptic plasticity and behavior in Angelman syndrome model mice. Kv4.2的活性依赖性降解有助于Angelman综合征模型小鼠的突触可塑性和行为。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-29 DOI: 10.1016/j.celrep.2025.115583

Jia-Hua Hu, Cole Malloy, Ying Liu, Jung M Park, Ashley Pratt, Meghyn Welch, Jonathan G Murphy, Daniel Abebe, Rose-Marie Karlsson, Heather A Cameron, Dax A Hoffman

{"title":"Activity-dependent degradation of Kv4.2 contributes to synaptic plasticity and behavior in Angelman syndrome model mice.","authors":"Jia-Hua Hu, Cole Malloy, Ying Liu, Jung M Park, Ashley Pratt, Meghyn Welch, Jonathan G Murphy, Daniel Abebe, Rose-Marie Karlsson, Heather A Cameron, Dax A Hoffman","doi":"10.1016/j.celrep.2025.115583","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115583","url":null,"abstract":"Angelman syndrome (AS) is a severe neurological disorder characterized by intellectual disability, absence of speech, spontaneous seizure, and motor dysfunction. The absence of functional maternally derived UBE3A protein is considered the primary cause of AS, yet the downstream signaling pathways remain elusive. Here, we show the voltage-gated K+ channel Kv4.2 as an activity-dependent substrate for UBE3A. We show that UBE3A binding of Kv4.2 at its N terminus, ubiquitinating residue K103, induces activity-induced Kv4.2 protein loss. In a mouse model of AS, we observe elevated Kv4.2 protein level and abolished kainic acid-induced Kv4.2 protein loss. Moreover, deficits in mEPSC frequency and spike-timing-dependent long-term potentiation, as well as certain behaviors including cognitive inflexibility found in AS mice, are rescued when bred with Kv4.2 conditional knockout mice. These findings indicate a UBE3A downstream pathway regulating plasticity and cognitive behaviors and provide potential targets for the treatment of AS.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115583"},"PeriodicalIF":7.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Functional characterization of the ATOH1 molecular subtype indicates a pro-metastatic role in small cell lung cancer. ATOH1分子亚型的功能特征表明在小细胞肺癌中具有促转移作用。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-29 DOI: 10.1016/j.celrep.2025.115603

Alessia Catozzi, Maria Peiris Pagès, Sam Humphrey, Mitchell Revill, Derrick Morgan, Jordan Roebuck, Yitao Chen, Bethan Davies-Williams, Kevin Brennan, A S Md Mukarram Hossain, Vsevolod J Makeev, Karishma Satia, Pagona P Sfyri, Melanie Galvin, Darryl Coles, Alice Lallo, Simon P Pearce, Alastair Kerr, Lynsey Priest, Victoria Foy, Mathew Carter, Rebecca Caeser, Joseph M Chan, Charles M Rudin, Fiona Blackhall, Kristopher K Frese, Caroline Dive, Kathryn L Simpson

{"title":"Functional characterization of the ATOH1 molecular subtype indicates a pro-metastatic role in small cell lung cancer.","authors":"Alessia Catozzi, Maria Peiris Pagès, Sam Humphrey, Mitchell Revill, Derrick Morgan, Jordan Roebuck, Yitao Chen, Bethan Davies-Williams, Kevin Brennan, A S Md Mukarram Hossain, Vsevolod J Makeev, Karishma Satia, Pagona P Sfyri, Melanie Galvin, Darryl Coles, Alice Lallo, Simon P Pearce, Alastair Kerr, Lynsey Priest, Victoria Foy, Mathew Carter, Rebecca Caeser, Joseph M Chan, Charles M Rudin, Fiona Blackhall, Kristopher K Frese, Caroline Dive, Kathryn L Simpson","doi":"10.1016/j.celrep.2025.115603","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115603","url":null,"abstract":"Molecular subtypes of small cell lung cancer (SCLC) have been described based on differential expression of the transcription factors (TFs) ASCL1, NEUROD1, and POU2F3 and immune-related genes. We previously reported an additional subtype based on expression of the neurogenic TF ATOH1 within our SCLC circulating tumor cell-derived explant (CDX) model biobank. Here, we show that ATOH1 protein is detected in 7 of 81 preclinical models and 16 of 102 clinical samples of SCLC. In CDX models, ATOH1 directly regulates neurogenesis and differentiation programs, consistent with roles in normal tissues. In ex vivo cultures of ATOH1+ CDXs, ATOH1 is required for cell survival. In vivo, ATOH1 depletion slows tumor growth and suppresses liver metastasis. Our data validate ATOH1 as a bona fide lineage-defining TF of SCLC with cell survival and pro-metastatic functions. Further investigation exploring ATOH1-driven vulnerabilities for targeted treatment with predictive biomarkers is warranted.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115603"},"PeriodicalIF":7.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Genome of a stage-dependent cave-dwelling frog reveals the genetic mechanism of an extremely divergent biphasic life cycle. 一个阶段依赖穴居青蛙的基因组揭示了一个极端不同的双相生命周期的遗传机制。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-29 DOI: 10.1016/j.celrep.2025.115640

Ningning Lu, Wei Zhu, Chen-Yang Tang, Chaochao Yan, Qiheng Chen, Wei Wu, Liming Chang, Jianping Jiang, Jia-Tang Li, Bin Wang

{"title":"Genome of a stage-dependent cave-dwelling frog reveals the genetic mechanism of an extremely divergent biphasic life cycle.","authors":"Ningning Lu, Wei Zhu, Chen-Yang Tang, Chaochao Yan, Qiheng Chen, Wei Wu, Liming Chang, Jianping Jiang, Jia-Tang Li, Bin Wang","doi":"10.1016/j.celrep.2025.115640","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115640","url":null,"abstract":"Cave-dwelling species offer unique insights into adaptive evolution. The stage-dependent cave frog, Oreolalax rhodostigmatus (Orho), exhibits troglomorphic traits as a tadpole in Karst caves, transitioning to a troglophilic/trogloxenic lifestyle after metamorphosis, characterized by developed pigment and eyes. We present the Orho genome (3.16 Gb, 26,192 protein-coding genes), revealing extensive expansion and positive selection in gene families associated with olfactory, taste, visual, and pain perceptions. Orho tadpoles exhibit suppressed visual function while retaining crystalline lens development. Adult eyes demonstrate high light-induced plasticity in the visual cycle. Orho tadpoles display both developmental and light-induced melanogenesis, which is associated with distinctive tyrosinases. A stage-dependent amphibian-specific tyrosinase subfamily, reported here, underpins their ontogenetic pigmentation. Additionally, prominent hepatic fat storage and genetic/transcriptional variations in lipid metabolism genes characterize tadpole development. These findings unveil the molecular mechanisms behind Orho's stage-dependent cave adaptation, which differs mechanistically from cavefishes, offering valuable insights into the highly divergent biphasic life cycle.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115640"},"PeriodicalIF":7.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Synaptic vesicle fusion promotes phosphatidylinositol 4-phosphate synthesis for efficient synaptic transmission. 突触囊泡融合促进磷脂酰肌醇4-磷酸合成，以实现有效的突触传递。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-28 DOI: 10.1016/j.celrep.2025.115634

Tomofumi Yoshida, Hiroyuki Kawano, Jumpei Omi, Tetsuya Hori, Yutaka Kobayashi, Naoto Saitoh, Junken Aoki, Shigeo Takamori

{"title":"Synaptic vesicle fusion promotes phosphatidylinositol 4-phosphate synthesis for efficient synaptic transmission.","authors":"Tomofumi Yoshida, Hiroyuki Kawano, Jumpei Omi, Tetsuya Hori, Yutaka Kobayashi, Naoto Saitoh, Junken Aoki, Shigeo Takamori","doi":"10.1016/j.celrep.2025.115634","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115634","url":null,"abstract":"Efficient synaptic vesicle (SV) recycling is essential for sustaining synaptic transmission. While the multiple roles of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in SV recycling are well documented, presynaptic regulation of phosphatidylinositol 4-phosphate (PI(4)P) synthesis and its potential role in SV recycling remain poorly understood. Here, we identify phosphatidylinositol 4-kinase IIIα (PI4KIIIα) as the key enzyme responsible for both the maintenance and activity-dependent production of presynaptic PI(4)P. Notably, we find that SVs are nearly devoid of PI(4)P and PI(4,5)P2 but are rich in phosphatidylinositol (PI) and that PI(4)P synthesis is triggered upon SV fusion as vesicular PI is delivered to the plasma membrane. Furthermore, when PI(4)P levels are selectively reduced without affecting basal PI(4,5)P2 levels, SV exo-endocytosis is significantly impaired, primarily due to reduced conductivity of voltage-gated Ca2+ channels. This reveals a PI(4,5)P2-independent homeostatic mechanism in which continuous PI(4)P production, driven by SV fusion, sustains efficient synaptic transmission.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115634"},"PeriodicalIF":7.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Extracellular vesicle-mediated plant miRNA trafficking regulates viral infection in insect vector. 细胞外囊泡介导的植物miRNA转运调控昆虫载体的病毒感染。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-27 DOI: 10.1016/j.celrep.2025.115635

Qian Wang, Hong Lu, Xiaoyue Fan, Jiaming Zhu, Jianfei Shi, Wan Zhao, Yan Xiao, Yongyu Xu, Jinfeng Chen, Feng Cui

{"title":"Extracellular vesicle-mediated plant miRNA trafficking regulates viral infection in insect vector.","authors":"Qian Wang, Hong Lu, Xiaoyue Fan, Jiaming Zhu, Jianfei Shi, Wan Zhao, Yan Xiao, Yongyu Xu, Jinfeng Chen, Feng Cui","doi":"10.1016/j.celrep.2025.115635","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115635","url":null,"abstract":"Extracellular vesicle (EV)-mediated small RNA trafficking plays an important role in intercellular and interspecies communication. Plant arboviruses keep homeostasis in insect vectors, thus ensuring vector survival and viral transmission. How plant EV-mediated cross-kingdom RNA interference participates in viral infection in insect vectors remains unknown. Here, we successfully isolate rice EVs and identify a batch of microRNAs (miRNAs) encapsulated in EVs. Two EV-enriched rice miRNAs, Osa-miR159a.1-1 and Osa-miR167a, are transported into midgut epithelial cells of small brown planthopper, which is a competent vector of rice stripe virus (RSV). Osa-miR159a.1-1 elevates the expression of a phospholipase C by enhancing its mRNA stability, inducing the downstream CSL expression to inhibit apoptosis for the benefit of RSV replication. On the other hand, Osa-miR167a directly binds RSV RdRp to suppress viral replication. This differential regulation of EV-mediated cross-kingdom RNA interference contributes to arbovirus homeostasis in insect vectors and the following efficient transmission.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115635"},"PeriodicalIF":7.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Staphylococcus aureus promotes strain-dependent immunopathology during cutaneous leishmaniasis through induction of IL-1β. 金黄色葡萄球菌通过诱导IL-1β促进皮肤利什曼病期间的菌株依赖免疫病理。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-27 DOI: 10.1016/j.celrep.2025.115624

Victoria Lovins, Camila Farias Amorim, Nélida Robles, Sofía Murga-Garrido, Jamie Ting-Chun Pan, Tej P Singh, Erin DeNardo, Lucas P Carvalho, Edgar M Carvalho, Phillip Scott, Elizabeth A Grice

{"title":"Staphylococcus aureus promotes strain-dependent immunopathology during cutaneous leishmaniasis through induction of IL-1β.","authors":"Victoria Lovins, Camila Farias Amorim, Nélida Robles, Sofía Murga-Garrido, Jamie Ting-Chun Pan, Tej P Singh, Erin DeNardo, Lucas P Carvalho, Edgar M Carvalho, Phillip Scott, Elizabeth A Grice","doi":"10.1016/j.celrep.2025.115624","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115624","url":null,"abstract":"Cutaneous leishmaniasis is a parasitic infection that causes a spectrum of pathology ranging from single, self-healing lesions to disfiguring chronic wounds. In severe disease, uncontrolled inflammation exacerbates tissue damage and delays healing, though the contributing factors are unclear. We previously observed that delayed healing was associated with Staphylococcus aureus in the lesional microbiota of patients with cutaneous leishmaniasis. To investigate how S. aureus impacts immunopathology during leishmania infection, we established a murine model of S. aureus colonization with clinical isolates followed by Leishmania infection. S. aureus triggered early production of interleukin (IL)-1β during Leishmania infection, which was critical for neutrophil recruitment and cutaneous inflammation. S. aureus isolates differentially induced IL-1β and neutrophil recruitment, and isolates that induced greater neutrophil recruitment were resistant to neutrophil killing and persisted longer. We reveal a mechanism whereby S. aureus mediates immunopathology during cutaneous leishmaniasis, suggesting IL-1β as a promising immunomodulatory target for non-healing infections.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115624"},"PeriodicalIF":7.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors. 核斑点中的TAF2缩聚将基础转录因子TFIID与RNA剪接因子联系起来。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-26 DOI: 10.1016/j.celrep.2025.115616

Tanja Bhuiyan, Niccolò Arecco, Paulina Karen Mendoza Sanchez, Juhyeong Kim, Carsten Schwan, Sophie Weyrauch, Sheikh Nizamuddin, Andrea Prunotto, Mehmet Tekman, Martin L Biniossek, Bettina Knapp, Stefanie Koidl, Friedel Drepper, Pitter F Huesgen, Robert Grosse, Thorsten Hugel, Sebastian J Arnold

{"title":"TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing factors.","authors":"Tanja Bhuiyan, Niccolò Arecco, Paulina Karen Mendoza Sanchez, Juhyeong Kim, Carsten Schwan, Sophie Weyrauch, Sheikh Nizamuddin, Andrea Prunotto, Mehmet Tekman, Martin L Biniossek, Bettina Knapp, Stefanie Koidl, Friedel Drepper, Pitter F Huesgen, Robert Grosse, Thorsten Hugel, Sebastian J Arnold","doi":"10.1016/j.celrep.2025.115616","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115616","url":null,"abstract":"TFIID is an essential basal transcription factor, crucial for RNA polymerase II (pol II) promoter recognition and transcription initiation. The TFIID complex consists of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs) that contain intrinsically disordered regions (IDRs) with currently unknown functions. Here, we show that a conserved IDR drives TAF2 to nuclear speckle condensates independently of other TFIID subunits. Quantitative mass spectrometry analyses reveal TAF2 proximity to RNA splicing factors including specific interactions of the TAF2 IDR with SRRM2 in nuclear speckles. Deleting the IDR from TAF2 does not majorly impact global gene expression but results in changes of alternative splicing events. Further, genome-wide binding analyses suggest that the TAF2 IDR impedes TAF2 promoter association by guiding TAF2 to nuclear speckles. This study demonstrates that an IDR within the large multiprotein complex TFIID controls nuclear compartmentalization and thus links distinct molecular processes, namely transcription initiation and RNA splicing.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115616"},"PeriodicalIF":7.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Functional-based parcellation of the mouse prefrontal cortex for network perturbation analysis. 基于功能的小鼠前额皮质网络摄动分析。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-25 DOI: 10.1016/j.celrep.2025.115622

Iurii Savvateev, Christina Grimm, Marija Markicevic, Joanes Grandjean, David Sastre, Alessandro Gozzi, Nicole Wenderoth, Rafael Polania, Valerio Zerbi

{"title":"Functional-based parcellation of the mouse prefrontal cortex for network perturbation analysis.","authors":"Iurii Savvateev, Christina Grimm, Marija Markicevic, Joanes Grandjean, David Sastre, Alessandro Gozzi, Nicole Wenderoth, Rafael Polania, Valerio Zerbi","doi":"10.1016/j.celrep.2025.115622","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115622","url":null,"abstract":"The prefrontal cortex (PFC) is a brain region involved in higher-order cognitive processes such as attention, emotional regulation, and social behavior. However, the delineation of distinct subdivisions within the mouse PFC and their contributions to the broader brain network function remain debated. This study utilizes resting-state functional magnetic resonance imaging (MRI) from a cohort of 100 C57BL/6J wild-type mice to derive the functional connectivity (FC)-based parcellation of the mouse PFC with voxel resolution. Our findings reveal clusters that deviate from the established anatomical subdivisions within the cingulate and prelimbic areas while aligning in infralimbic and orbital cortices. Upon the chemogenetic perturbation of one of the clusters, FC perturbations occur only within the functional network linked to the targeted cluster and do not spread to neighboring anatomical areas or functional clusters. We propose FC-based parcellation as a valuable approach for tracking the site of activation and network impact of neurostimulation strategies.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115622"},"PeriodicalIF":7.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Peroxisomes are critical for a unique metabolic demand and survival of alveolar macrophages. 过氧化物酶体是肺泡巨噬细胞独特的代谢需求和生存的关键。

IF 7.5 1区生物学

Cell reports Pub Date : 2025-04-25 DOI: 10.1016/j.celrep.2025.115623

Mai Matsushita, Jonathan Muri, Ivan Berest, Fengqi Li, Huan Liu, Basak Corak, Nicola Zamboni, Joerg Buescher, Alaa Othman, Mauro Corrado, Jovana Cupovic, Sabine Werner, Werner Kovacs, Manfred Kopf

{"title":"Peroxisomes are critical for a unique metabolic demand and survival of alveolar macrophages.","authors":"Mai Matsushita, Jonathan Muri, Ivan Berest, Fengqi Li, Huan Liu, Basak Corak, Nicola Zamboni, Joerg Buescher, Alaa Othman, Mauro Corrado, Jovana Cupovic, Sabine Werner, Werner Kovacs, Manfred Kopf","doi":"10.1016/j.celrep.2025.115623","DOIUrl":"https://doi.org/10.1016/j.celrep.2025.115623","url":null,"abstract":"Tissue-resident macrophages (TRMs) populate throughout various tissues, and their homeostatic metabolism is heavily influenced by these microenvironments. Peroxisomes are organelles that contribute to lipid metabolism. However, the involvement of these organelles in the bioenergetics of TRMs remains undetermined. We conducted a developmental screen of TRMs using a conditional peroxisomal biogenesis factor 5 (Pex5) knockout mouse model that lacks functional peroxisomes in all immune cell subsets. Pulmonary alveolar macrophages (AMs) appeared as the only subset of TRMs that required functional peroxisomes for their development. Pex5 deficiency resulted in reduced AM survival due to increased sensitivity to lipotoxicity, in line with an excess accumulation of ceramides. The absence of peroxisomes had a significant effect on overall mitochondrial fitness and altered their metabolic program, allowing them to engage in glycolysis in addition to oxidative phosphorylation. Our results revealed that AMs have a unique metabolic regulation, where peroxisomes play a central role in their homeostatic development and maintenance.","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"44 5","pages":"115623"},"PeriodicalIF":7.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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