{"title":"Controlling scissors during DNA repair of UV light-induced damage.","authors":"Patricia L Opresko,Orlando D Schärer","doi":"10.1083/jcb.202606004","DOIUrl":"https://doi.org/10.1083/jcb.202606004","url":null,"abstract":"Nucleotide excision repair is essential for genome stability; however, enzymatic scissors that remove damage must be tightly regulated to prevent erroneous DNA cleavage. In this issue, Muniesa-Vargas et al. (https://doi.org/10.1083/jcb.202602121) used live-cell imaging to uncover how cutting DNA by XPG endonuclease is controlled during repair.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"38 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432899","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}
{"title":"Rag GTPases and mTORC1 regulate intestinal stem cell activity in response to nutrient availability.","authors":"Weikang Fan,Churui Ge,Chunmei Niu,Shuang Liu,Peng Wang,Heng Li,Yang Cheng,Yingying Lu,Youheng Wei","doi":"10.1083/jcb.202510172","DOIUrl":"https://doi.org/10.1083/jcb.202510172","url":null,"abstract":"The intestinal epithelium, predominantly composed of enterocytes (ECs), integrates dietary cues to regulate intestinal stem cell (ISC) activity and maintain intestinal homeostasis. However, the underlying mechanisms remain incompletely understood. Here, we demonstrate the functions of essential nutrient-sensing mediators Rag GTPases and mTORC1 on Drosophila ISC activity. Inhibition of Rag GTPases in ECs triggers Mitf activation, which subsequently induces Upd3 expression to non-cell autonomously increase the ISC proliferation and differentiation through stimulating the JAK-STAT pathway. Inactivation of mTORC1 in ECs also activates the Upd3-JAK-STAT axis and increases ISC activity, but through a Mitf-independent mechanism. Moreover, in contrast to mTORC1 inactivation blocking ISC proliferation and differentiation, depletion of Rag GTPases in ISCs shows no obvious cell autonomous effect on ISC activity. Consistent with inhibition of the nutrient-responsive pathway in ECs promoting ISC proliferation, long-term nutrient starvation enhances ISC activity and Upd3 expression. Together, our findings reveal a nutrient-sensing regulatory network that controls ISC proliferation involving the Rag GTPases-Mitf axis and mTORC1 activity.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"60 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429106","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}
{"title":"PISD acts as a switch between lipophagy and fatty acid transfer to mitochondria.","authors":"Hanbing Xue,Xingwen Hu,Zhenni Yang,Yiqing Cao,Qi Zhu,Hongyu Zhao,Xiaoli Ma,Tianxin Lei,Dian Zhuang,Jing Zheng,Siqi Guo,Xiaochuan Fu,Ka Kit Chung,Pingsheng Liu,Xiaohong Zhuang,Zhengyu Liang,Sicong He,Hui Jiang,Yan G Zhao","doi":"10.1083/jcb.202605090","DOIUrl":"https://doi.org/10.1083/jcb.202605090","url":null,"abstract":"Fatty acids (FAs) are transported from lipid droplets (LDs) to mitochondria for β-oxidation during cell starvation. Starvation also triggers engulfment of LDs by autophagosomes and their subsequent degradation by lysosomes (lipophagy). The mechanisms coordinating these pathways remain unclear. Here, we demonstrate that PISD-LD, an LD-localized isoform of phosphatidylserine decarboxylase, facilitates FA transfer while inhibiting lipophagy. PISD-LD mediates LD-mitochondrion (LD-mito) contacts via interaction with mitochondrial PISD. In PISD-LD KD cells, LDs are larger, and FA trafficking and mitochondrial FA β-oxidation are suppressed. The lipid transfer proteins ATG2A/B are recruited by PISDs to mediate FA transfer from LDs to mitochondria. Disruption of PISD-LD-mediated LD-mito contacts activates lipophagy, aiding LD degradation. PISD-LD binds the lipophagy receptor Spartin and inhibits lipophagy by impeding Spartin-LC3 interaction. PISD-LD also regulates LD-mito contacts and lipid metabolism in mouse liver. Thus, PISD-LD serves as a switch between LD-to-mitochondrion FA transfer and lipophagy, ensuring efficient energy production.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"447 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428920","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}
{"title":"Receptor-mediated Golgi retention of Fam20 kinases tunes secretome phosphorylation during lactation.","authors":"Xiaotong Yang,Jueyin He,Xiulan Chen,Xi'e Wang,Chenyun Hu,Xuqian Zhao,Xinxin Chen,Jiaojiao Yu,Ping Liu,Jifeng Wang,Xi Wang,Junjie Hu,Mei Ding,Fuquan Yang,Chih-Chen Wang,Lei Wang","doi":"10.1083/jcb.202507107","DOIUrl":"https://doi.org/10.1083/jcb.202507107","url":null,"abstract":"Fam20C, the first protein kinase identified in the secretory pathway, governs the majority phosphorylation of the secretome. Although Fam20C has a high propensity for secretion, its kinase activity occurs intracellularly. How Fam20C clients are phosphorylated inside cells remains elusive. Here, we demonstrate that the pseudokinase Fam20A forms a heterocomplex with Fam20C on the Golgi membrane, anchoring the cleaved, mature form of Fam20C within the Golgi. Their Golgi localization is promoted by a set of cargo receptors ERGIC2 and ERGIC3, which drive the ER-to-Golgi transport of Fam20A-Fam20C. Importantly, both ERGIC2 and ERGIC3 are upregulated in the mammary gland during lactation, and Ergic2 or Ergic3 knockout mice display global changes in secretome phosphorylation, less phosphorylated β-casein in milk, and deficiency in offspring growth. Our findings uncover a previously unrecognized mechanism for the spatiotemporal regulation of Fam20 kinases, crucial for efficient phosphorylation of secretory proteins during lactation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"39 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429107","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}
Mami Sato,Florencio Porto Freitas,José Pedro Friedmann Angeli
{"title":"More gas, fewer brakes: Mitochondria withhold CoQ at the cost of ferroptosis defense.","authors":"Mami Sato,Florencio Porto Freitas,José Pedro Friedmann Angeli","doi":"10.1083/jcb.202606160","DOIUrl":"https://doi.org/10.1083/jcb.202606160","url":null,"abstract":"Coenzyme Q (CoQ or ubiquinone) is an essential cofactor for mitochondrial energy production and a vital radical-trapping antioxidant that maintains membrane integrity. Additionally, CoQ shares an early biosynthetic pathway with cholesterol biosynthesis. In this issue, Ndoci et al. (https://doi.org/10.1083/jcb.202507174) reveal a regulatory system that preserves mitochondrial CoQ levels when the mevalonate pathway is impaired, though this prioritization leaves cells vulnerable to oxidative stress.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"11 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429108","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}
{"title":"Inorganic phosphate rapidly switches the stability of Arp2/3-induced actin branches.","authors":"Jiu Xiao,Foad Ghasemi,Adrien Schahl,Miroslav Mladenov,Rebecca Pagès,Matthieu Chavent,Michael Way,Luyan Cao,Guillaume Romet-Lemonne,Antoine Jégou","doi":"10.1083/jcb.202605018","DOIUrl":"https://doi.org/10.1083/jcb.202605018","url":null,"abstract":"Actin filaments often appear as branches, nucleated by the Arp2/3 complex. Arp2 and Arp3 are ATPases, which adopt different nucleotide-dependent conformations. We investigated how the nucleotide state of mammalian Arp2/3 complexes affects branch stability, by applying mechanical load. Branch junctions are 30-fold more stable when Arp2/3 is in the ADP-inorganic phosphate (Pi) rather than the ADP state. Pi is in rapid equilibrium with the ADP-Arp2/3 complex at the branch junction (release rate 0.2 s-1). Upon branch dissociation, Arp2/3 complexes remaining attached to the mother filament in the ADP-Pi state are 100-fold more stable, release their phosphate slowly (0.05 s-1), and can regrow branches without reloading ATP. Glia maturation factor (GMF) accelerates the dissociation of surviving ADP-Arp2/3 complexes, but does not prevent branch regrowth at physiological ATP concentration. Cortactin stabilizes branches and enhances renucleation. Neither GMF nor cortactin affects branch stability and renucleation of ADP-Pi-Arp2/3. Overall, these results identify Pi in the Arp2/3 complex as a critical regulator of branched actin network stability.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"230 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408596","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}
{"title":"Skin without fibroblasts: Rethinking epidermal-dermal dependence.","authors":"Emanuel Rognoni","doi":"10.1083/jcb.202606030","DOIUrl":"https://doi.org/10.1083/jcb.202606030","url":null,"abstract":"Epidermal stem cell maintenance depends on complex niche signalling. In this issue Gaeta, Du et al. (https://doi.org/10.1083/jcb.202507165) show that substantial dermal fibroblast depletion has surprisingly minimal effects on epidermal proliferation and skin function during development and adult homeostasis.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"34 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408597","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}
{"title":"aPKC exclusion from the apical cortex in enteroblasts maintains stem cell homeostasis in Drosophila.","authors":"Yasushi Izumi,Mikio Furuse","doi":"10.1083/jcb.202509240","DOIUrl":"https://doi.org/10.1083/jcb.202509240","url":null,"abstract":"Proper control of stem cell behavior is crucial for maintaining tissue homeostasis. In the Drosophila midgut, smooth septate junction (sSJ)-associated proteins play a crucial role in regulating intestinal stem cell (ISC) proliferation via atypical PKC (aPKC) activity. Here, we investigate the underlying mechanism. We found that aPKC in the apical cortex diminishes during enteroblast differentiation, in accordance with the apical accumulation of sSJ proteins. In sSJ protein-deficient conditions, aPKC remained in the apical cortex in enteroblasts, accompanied by ISC overproliferation. Manipulation of Kibra, an activator of the Hippo pathway with aPKC-binding properties, affected sSJ proteins depletion-induced ISC overproliferation in an aPKC-binding domain-dependent manner, revealing a link between aPKC and the Hippo- and/or Misshapen-Yorkie pathway in ISC proliferation. This study provides novel insights into the mechanism underlying stem cell regulation, in which an antagonistic interaction between aPKC and junctional proteins in differentiating progenitors is involved.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393330","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}
{"title":"Intercellular mitochondrial transfer and trans-mitophagy in response to protein import dysfunction.","authors":"Emily Glover,Beth Wiseman,Celyn Dugdale,Charlie Humphery,Lorena Sueiro Ballesteros,Lorna Hodgson,Kevin Wilkinson,Ian Collinson","doi":"10.1083/jcb.202511211","DOIUrl":"https://doi.org/10.1083/jcb.202511211","url":null,"abstract":"Mitochondrial protein import is critical for organelle biogenesis, maintenance, and regeneration-essential for cellular homeostasis. Import dysfunction compromises cellular energy supplies, which is damaging to cells, particularly those with high energetic demands like neurons. Previously, we have shown that import failure is rescued by intercellular mitochondrial transfer (IMT) via tunnelling nanotubes (TNTs) however, the fate of the transferred mitochondria and the mechanistic basis for rescue were unresolved. Here, we show that bidirectional mitochondrial trafficking between cells harboring import-defective and import-competent mitochondria is distinct in terms of their regulation and ensuing consequences. Transferred import-defective mitochondria are highly fragmented and destined for canonical lysosomal degradation. In contrast, reactive oxygen species (ROS)-producing mitochondria at the periphery of cells with import-competent mitochondria are transferred into neighboring cells undergoing import failure. These new arrivals then accumulate within previously uncharacterized \"mitochondrial degradation bodies\" (MDBs). We speculate that the cooperation of these distinct cases of TNT-mediated conventional and noncanonical \"trans-mitophagy\" instigates mitochondrial regeneration, and thereby rescues mitochondrial function.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"97 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393329","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}
{"title":"Early architects: Eosinophils promote postnatal development of the small intestinal villus structure.","authors":"Nicola Laura Diny","doi":"10.1083/jcb.202605117","DOIUrl":"10.1083/jcb.202605117","url":null,"abstract":"<p><p>Smooth muscle cells in the intestinal villus form early postnatally and aid the uptake of dietary fats. In this issue, Petrova et al. (https://doi.org/10.1083/jcb.202505012) describe a second postnatal wave of smooth muscle cell formation from PDGFRβ+ perivascular cells induced by eosinophil-derived TGFβ.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 7","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198936","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}