Cell Chemical Biology最新文献_第9页

Licensed to pore: Gasdermins in action 授权毛孔：Gasdermins在行动。

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-07-16 Epub Date: 2026-06-01 DOI: 10.1016/j.chembiol.2026.05.001

Natália Ketelut-Carneiro, Anukriti Mathur, Katherine A. Fitzgerald

{"title":"Licensed to pore: Gasdermins in action","authors":"Natália Ketelut-Carneiro, Anukriti Mathur, Katherine A. Fitzgerald","doi":"10.1016/j.chembiol.2026.05.001","DOIUrl":"10.1016/j.chembiol.2026.05.001","url":null,"abstract":"<div><div>Gasdermins (GSDMs) are a conserved family of pore-forming proteins that execute pyroptosis. Proteolytic activation of GSDMs by caspases, granzymes, or microbial enzymes liberates the N-terminal domain, which oligomerizes and inserts into membranes to form pores, releasing interleukin-1 cytokines, alarmins, and cytosolic contents. Recent structural and biochemical studies have provided mechanistic insight into GSDM cleavage, lipid recognition, and post-translational modifications, which regulate pore formation and pyroptosis. GSDMs sit at the nexus of host defense and pathology, simultaneously constraining pathogens while amplifying tissue injury, septic shock, and chronic inflammation. In sterile contexts, GSDMs contribute to autoimmunity and barrier injury while paradoxically supporting tissue regeneration. Their roles in cancer are highly context-dependent, spanning across tumor suppression, immune activation, and immune evasion. Emerging therapeutic strategies, including small-molecule inhibitors and agonists, underscore the translational potential of targeting GSDMs. This review integrates mechanistic, physiological, and translational advances defining GSDMs as versatile regulators of immunity and disease.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 7","pages":"Pages 982-1004"},"PeriodicalIF":9.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142000","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

PANoptosis in life and death across cell types: From innate immunity to therapeutic implications 跨细胞类型的生与死：从先天免疫到治疗意义

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-07-16 DOI: 10.1016/j.chembiol.2026.06.007

Kristine E. Zengeler, Rebecca E. Tweedell, Thirumala-Devi Kanneganti

{"title":"PANoptosis in life and death across cell types: From innate immunity to therapeutic implications","authors":"Kristine E. Zengeler, Rebecca E. Tweedell, Thirumala-Devi Kanneganti","doi":"10.1016/j.chembiol.2026.06.007","DOIUrl":"10.1016/j.chembiol.2026.06.007","url":null,"abstract":"<div><div>Innate immune cell death is a fundamental mechanism used by organisms to respond to perturbations, including infection, tissue damage, and cancer. However, excessive cell death can be inflammatory and cause pathology. PANoptosis has emerged as a distinct, lytic, inflammatory cell death pathway initiated by innate immune sensors and driven by caspases and receptor-interacting protein kinases through multiprotein PANoptosome complexes. Genetic, biochemical, and imaging evidence initially identified PANoptosis in macrophages but now indicates that it operates across diverse immune, non-immune, and cancer cell types, where it drives host defense, inflammation, and pathology. In this review, we critically evaluate current evidence for PANoptosis as a unique and central cell death pathway across cell types and disease contexts, elucidating the key molecular mechanisms that govern its activation. We discuss emerging insights into PANoptosome biology, the physiological and pathological functions of PANoptosis, and how cell type-specific regulation shapes disease outcomes. Finally, we highlight the therapeutic opportunities and challenges associated with the cell-selective modulation of PANoptosis to improve treatment of infectious, inflammatory, and malignant diseases.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 7","pages":"Pages 1021-1037"},"PeriodicalIF":9.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Mechanism and regulation of programmed cell death in aging-related diseases 衰老相关疾病中细胞程序性死亡的机制与调控。

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-07-16 Epub Date: 2026-07-06 DOI: 10.1016/j.chembiol.2026.06.005

Xingxing Xie, Daichao Xu

引用次数: 0

Metabolic underpinnings of cuproptosis 铜突起的代谢基础。

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-07-16 Epub Date: 2026-05-14 DOI: 10.1016/j.chembiol.2026.04.009

Dadi Jiang, Li Zhuang, Albert C. Koong, Boyi Gan

引用次数: 0

CXCR4-EGFR heteromers show ligand-dependent changes in conformation and signaling. CXCR4-EGFR异构体在构象和信号传导方面表现出配体依赖性的变化。

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-07-14 DOI: 10.1016/j.chembiol.2026.06.008

Dehan Comez, Stephanie M Anbuhl, Simon Platt, Oliver C Isaac, Noemi Karsai, Robert Markus, Marco Siderius, Martine J Smit, Raimond Heukers, Laura E Kilpatrick, Stephen J Hill

引用次数: 0

Assessment of mitochondrial lipid peroxidation in cells and zebrafish using a targeted mass spectrometry probe. 使用靶向质谱探针评估细胞和斑马鱼的线粒体脂质过氧化。

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-06-30 DOI: 10.1016/j.chembiol.2026.05.015

Shinpei Uno, Stuart T Caldwell, Hiran A Prag, Chak Shun Yu, Lucie J Lamačová, María Torres-López, Andrew M James, Ana Lopez, Taylor A Woetzel, Angeleen Fleming, David C Rubinsztein, Richard C Hartley, Michael P Murphy

{"title":"Assessment of mitochondrial lipid peroxidation in cells and zebrafish using a targeted mass spectrometry probe.","authors":"Shinpei Uno, Stuart T Caldwell, Hiran A Prag, Chak Shun Yu, Lucie J Lamačová, María Torres-López, Andrew M James, Ana Lopez, Taylor A Woetzel, Angeleen Fleming, David C Rubinsztein, Richard C Hartley, Michael P Murphy","doi":"10.1016/j.chembiol.2026.05.015","DOIUrl":"10.1016/j.chembiol.2026.05.015","url":null,"abstract":"<p><p>Mitochondrial lipid peroxidation is a major component of oxidative damage and is also thought to contribute to ferroptosis. Lipid peroxidation is generally assessed from the accumulation of oxidized end products, such as 4-hydroxynonenal (HNE). However, these report on damage throughout the cell and are affected by changes in how oxidized phospholipids are turned over. To overcome these constraints, we developed MitoLiPOX, a mitochondria-targeted mass spectrometry probe. Mitochondria targeting and detection sensitivity were achieved by incorporating a lipophilic triphenylphosphonium cation. Responsiveness to lipid peroxidation was brought about by building in a bis-allylic carbon-hydrogen bond mimic that, upon oxidation and processing, generated a single product, MitoLiPOX-OH. LC-MS/MS quantification of MitoLiPOX-OH followed by normalization to the amount of MitoLiPOX present enabled ratiometric quantification of mitochondrial lipid peroxidation. We then used MitoLiPOX to assess mitochondrial lipid peroxidation during ferroptosis in vitro and in zebrafish in vivo.</p>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358807","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

Mechanisms and interventions of epigenetic aging 表观遗传衰老的机制及干预措施

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-06-18 DOI: 10.1016/j.chembiol.2026.05.007

Qingqing Chu , Yihang Li , Zeming Wu , Jing Qu , Guang-Hui Liu

引用次数: 0

The molecular basis for nuclear pore destruction by a proximity-inducing molecular glue 邻近诱导分子胶破坏核孔的分子基础。

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-06-18 Epub Date: 2026-05-27 DOI: 10.1016/j.chembiol.2026.04.016

Stephen M. Hinshaw , Linjie Yuan , Md Abdullah Al Noman , Michael J. Martinez , Gianna M. Colombo , Brendan G. Dwyer , Wenzhi Ji , Bryan A. Romero , Ines Forrest , Joey Lu , Jing Bian , Trae B. Dunn , Ethan R. Garvin , Daniel Fernandez , Tinghu Zhang , Nathanael S. Gray , Steven M. Corsello

{"title":"The molecular basis for nuclear pore destruction by a proximity-inducing molecular glue","authors":"Stephen M. Hinshaw , Linjie Yuan , Md Abdullah Al Noman , Michael J. Martinez , Gianna M. Colombo , Brendan G. Dwyer , Wenzhi Ji , Bryan A. Romero , Ines Forrest , Joey Lu , Jing Bian , Trae B. Dunn , Ethan R. Garvin , Daniel Fernandez , Tinghu Zhang , Nathanael S. Gray , Steven M. Corsello","doi":"10.1016/j.chembiol.2026.04.016","DOIUrl":"10.1016/j.chembiol.2026.04.016","url":null,"abstract":"<div><div>Molecular glues that induce new protein interactions can be potent therapeutics. We and others recently discovered that the small molecule PRLX-93936 (PRLX), which was originally developed as an erastin derivative with antitumor activity, is a molecular glue that alters the substrate specificity of the TRIM21 ubiquitin ligase. PRLX causes TRIM21 to bind the nuclear pore protein NUP98, triggering nuclear pore complex (NPC) degradation. We present here the structural and biochemical basis of NUP98 recognition, finding that ternary complex assembly depends on the creation of a composite TRIM21-small molecule surface competent for NUP98 binding. A scarcity of direct small molecule-NUP98 contacts likely explains how multiple structurally diverse TRIM21 ligands can induce NPC degradation. We also report the discovery of an enhanced molecular glue, MAN-021, and describe its structure. Our findings provide a basis for rational development of next-generation small molecules with enhanced or differentiated activities.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 6","pages":"Pages 799-809.e10"},"PeriodicalIF":9.0,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040222","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

An extracellular, optogenetic antibody platform for stimulus-gated antigen recognition and modulation of cell behavior 一个细胞外的光遗传抗体平台，用于刺激门控抗原识别和细胞行为的调节。

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-06-18 Epub Date: 2026-05-07 DOI: 10.1016/j.chembiol.2026.04.006

Eury Kwon, Daseuli Yu, Jihwan Yu, Hyun-Jin Kim, Yeonji Jeong, Heung Kyu Lee, Won Do Heo

引用次数: 0

A defense-like route to gene transfer agent release 一种类似防御的基因转移剂释放途径。

IF 9 1区生物学

Cell Chemical Biology Pub Date : 2026-06-18 DOI: 10.1016/j.chembiol.2026.05.014

Franklin L. Nobrega

引用次数: 0