Nature Cell Biology最新文献_第10页

DNA nanodevices detect an acidic nanolayer on the lysosomal surface DNA纳米装置检测溶酶体表面的酸性纳米层

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-21 DOI: 10.1038/s41556-025-01855-y

Yutong Zhang, Meiqin Hu, Yaping Meng, Xin Wang, Fangqian Huang, Ping Li, Yuting Zhuo, Danzhen Chen, Zhimin Wang, Qiang Zhang, Hui Wu, Yao He, Yulin Du, Haoxing Xu, Liping Qiu, Weihong Tan

{"title":"DNA nanodevices detect an acidic nanolayer on the lysosomal surface","authors":"Yutong Zhang, Meiqin Hu, Yaping Meng, Xin Wang, Fangqian Huang, Ping Li, Yuting Zhuo, Danzhen Chen, Zhimin Wang, Qiang Zhang, Hui Wu, Yao He, Yulin Du, Haoxing Xu, Liping Qiu, Weihong Tan","doi":"10.1038/s41556-025-01855-y","DOIUrl":"10.1038/s41556-025-01855-y","url":null,"abstract":"Lysosomes maintain a highly acidic lumen to regulate H+-dependent hydrolase-mediated degradation, but how protons are ‘leaked’ out to regulate organellar functions through cytosolic effectors remains unknown. Here we developed DNA nanodevices on the cytosolic leaflet of lysosomal membranes to monitor juxta-organellar pH in cells. Unexpectedly, we revealed a radiating acidic layer (up to 21 nm in thickness) on the outer surface of all lysosomes, typically 0.2–0.7 pH units more acidic than the neutral cytosol. This acidic nanolayer is established and maintained primarily by TMEM175, a lysosomal H+ efflux channel associated with Parkinson’s disease. Activation of TMEM175 causes opposite pH changes on both sides of lysosomes; however, it is the juxta-lysosomal, not the luminal, acidity that determines lysosome positioning in cells with dynein adaptor RILP acting as a juxta-lysosomal pH sensor. Hence, through inside-out proton conduits, lysosomes create a steady acidic surrounding that acts as a nano-interface for cytosolic machineries to regulate organellar activities. Tan and colleagues develop DNA nanodevices to detect the pH of the lysosomal outer surface, observing an acidic layer generated by TMEM175 that regulates lysosome positioning in response to changes in juxta-lysosomal pH.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 2","pages":"285-295"},"PeriodicalIF":19.1,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005981","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

Publisher Correction: SLC2A1+ tumour-associated macrophages spatially control CD8+ T cell function and drive resistance to immunotherapy in non-small-cell lung cancer 发布者更正：SLC2A1+肿瘤相关巨噬细胞在非小细胞肺癌中空间控制CD8+ T细胞功能并驱动免疫治疗耐药性。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-19 DOI: 10.1038/s41556-026-01874-3

Lei Wang, Han Chu, Degao Chen, Yuxuan Wei, Jia Jia, Liqi Li, Linfeng He, Lina Peng, Fangfang Liu, Shanshan Huang, Zheng Jin, Dong Zhou, WenFeng Fang, Tao Jiang, Shouxia Xu, Xiaofang Ding, Haoyang Cai, Xindong Liu, Qingzhu Jia, Bo Zhu, Qian Chu

引用次数: 0

GPX4 mutation in neurodegeneration GPX4在神经变性中的突变

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-15 DOI: 10.1038/s41556-025-01862-z

Zhe Wang

引用次数: 0

Mitoxyperilysis as a distinct cell death type 丝裂细胞坏死是一种独特的细胞死亡类型

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-15 DOI: 10.1038/s41556-025-01861-0

Melina Casadio

引用次数: 0

Clocking intestinal absorption 肠道吸收计时

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-15 DOI: 10.1038/s41556-025-01865-w

Angela R. Parrish

引用次数: 0

Advancing monkey blastoids 进化中的猴胚

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-15 DOI: 10.1038/s41556-025-01857-w

Stylianos Lefkopoulos

引用次数: 0

Programmed mitophagy at the oocyte-to-zygote transition promotes lineage endurance 在卵母细胞到受精卵的转变过程中，程序化的有丝自噬促进了谱系的持久性。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-12 DOI: 10.1038/s41556-025-01854-z

Siddharthan B. Thendral, Sasha Bacot, Ian T. Ryde, Katherine S. Morton, Qiuyi Chi, Isabel W. Kenny-Ganzert, Joel N. Meyer, David R. Sherwood

{"title":"Programmed mitophagy at the oocyte-to-zygote transition promotes lineage endurance","authors":"Siddharthan B. Thendral, Sasha Bacot, Ian T. Ryde, Katherine S. Morton, Qiuyi Chi, Isabel W. Kenny-Ganzert, Joel N. Meyer, David R. Sherwood","doi":"10.1038/s41556-025-01854-z","DOIUrl":"10.1038/s41556-025-01854-z","url":null,"abstract":"The quality of mitochondria inherited from the oocyte determines embryonic viability, lifelong metabolic health of the progeny and lineage endurance. High levels of endogenous reactive oxygen species and exogenous toxicants pose threats to mitochondrial DNA (mtDNA) in fully developed oocytes. Deleterious mtDNA is commonly detected in mature oocytes, but is absent in embryos, suggesting the existence of a cryptic purifying selection mechanism. Here, we discover that in Caenorhabditis elegans, the onset of oocyte-to-zygote transition developmentally triggers a rapid mitophagy event. We show that mitophagy at oocyte-to-zygote transition (MOZT) requires mitochondrial fragmentation, the macroautophagy pathway and the mitophagy receptor FUNDC1, but not the prevalent mitophagy factors PINK1 and BNIP3. MOZT reduces the transmission of deleterious mtDNA and as a result, protects embryonic survival. Impaired MOZT drives the increased accumulation of mtDNA mutations across generations, leading to the extinction of descendant populations. Thus, MOZT represents a strategy that preserves mitochondrial health during the mother-to-offspring transmission and safeguards lineage continuity. Thendral et al. describe a mitophagic programme that removes deleterious mtDNA during the oocyte-to-zygote transition in Caenorhabditis elegans, promoting mitochondrial health and offspring survival. Loss of this mitophagy leads to mutant mtDNA accumulation.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 2","pages":"268-284"},"PeriodicalIF":19.1,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955978","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

RPA exhaustion activates SLFN11 to eliminate cells with heightened replication stress RPA耗竭激活SLFN11以消除复制应激升高的细胞。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-09 DOI: 10.1038/s41556-025-01852-1

Tyler H. Stanage, Shudong Li, Sandra Segura-Bayona, Aurora I. Idilli, Rhona Millar, Graeme Hewitt, Simon J. Boulton

{"title":"RPA exhaustion activates SLFN11 to eliminate cells with heightened replication stress","authors":"Tyler H. Stanage, Shudong Li, Sandra Segura-Bayona, Aurora I. Idilli, Rhona Millar, Graeme Hewitt, Simon J. Boulton","doi":"10.1038/s41556-025-01852-1","DOIUrl":"10.1038/s41556-025-01852-1","url":null,"abstract":"SLFN11 is epigenetically silenced and confers chemoresistance in half of all cancers. In response to replication stress, SLFN11 triggers translation shutdown and p53-independent apoptosis, but how DNA damage activates SLFN11 remains unclear. Here through CRISPR-based screens we implicate SLFN11 as the critical determinant of cisplatin sensitivity in cells lacking primase–polymerase (PrimPol)-mediated repriming. SLFN11 and the downstream integrated stress response uniquely promote cisplatin-driven apoptosis in PrimPol-deficient cells. We demonstrate that replication protein A (RPA) exhaustion and single-stranded DNA exposure trigger SLFN11 activation and cell death when PrimPol is inactivated. We further identify the USP1–WDR48 deubiquitinase complex as a positive modulator of SLFN11 activation in PrimPol-deficient cells, revealing an addiction to the Fanconi anaemia pathway to resolve cisplatin lesions. Finally, we demonstrate that rapid RPA exhaustion on chemical inhibition of DNA polymerase α activates SLFN11-dependent cell death. Together, our results implicate RPA exhaustion as a general mechanism to activate SLFN11 in response to heightened replication stress. Stanage et al. identify a role for transfer RNA nuclease SLFN11 in replication-stress-induced cell death in cisplatin-treated cells lacking PrimPol. SLFN11 is activated upon single-stranded DNA accumulation at stalled forks followed by replication protein A exhaustion and cell death.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"28 2","pages":"240-254"},"PeriodicalIF":19.1,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41556-025-01852-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937789","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

Immune evasion by macrophage-derived lactate 巨噬细胞衍生乳酸的免疫逃避。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-08 DOI: 10.1038/s41556-025-01842-3

He Ren, Leina Ma, Xiaoming Jiang, Zhimin Lu

引用次数: 0

Revealing high-resolution spatial metagenes from spatial transcriptomics 从空间转录组学揭示高分辨率空间宏基因组。

IF 19.1 1区生物学

Nature Cell Biology Pub Date : 2026-01-08 DOI: 10.1038/s41556-025-01848-x

引用次数: 0