Research articles

Mondal et al. report that autophagy inhibition promotes p63 activation and metastasis in breast cancer. This process depends on NBR1, which forms cytoplasmic p62/SQSTM1 condensates that sequester the ITCH ubiquitin ligase and prevents p63 degradation.

Banerjee et al. report that the Vps13-like lipid transport protein BLTP2 regulates plasma membrane fluidity by maintaining phosphatidylethanolamine homeostasis. BLTP2 also facilitates breast cancer cell growth, suggesting a separate role in tumorigenesis.

Wu et al. demonstrate that REM transcription factors and GDE1 guide RNA polymerase IV to specific genomic loci, establishing a DNA sequence-dependent mechanism for siRNA biogenesis and DNA methylation patterning.

Li et al. uncover a lysosomal surveillance response whereby intestinal lumen deacidification induces a transcriptional programme that boosts lysosomal activity and improves protein aggregate clearance in multiple worm disease models, extending healthspan.

Zhang et al. show that YAP binds to TDP-43 to promote TDP-43 multimerization and phase separation. YAP and TDP-43 may co-localize in multiple cell types in oxidative stress and in brain samples from individuals with amyotrophic lateral sclerosis.

Zhang et al. provide evidence that, during meiosis, recombination proteins assemble into active droplets, the coarsening of which partially explains the phenomenon of crossover interference.

Clarke et al. identify chromatin factor ZNF280A, which is recruited to damaged chromatin where it promotes long-range DNA-end resection. Loss of ZNF280A is linked to genome instability in patients with 22q11.2 distal deletion syndrome.

Sassano et al. identify endoplasmic reticulum–mitochondria contact sites as the intracellular ___location where phospholipid peroxidation first occurs to promote ferroptosis. Manipulating these contact sites dictates ferroptosis sensitivity in breast cancer.

Kletter et al. show that cell state-specific cytoplasmic density controls spindle architecture and scaling in neural differentiation, suggesting that the physical properties of the cytoplasm are a determinant in organelle size control.

Sharma, Jiao and colleagues report glycosylation of small RNAs within exosomes and propose a glycosylation-dependent mechanism for RNA targeting into exosomes, which may influence intercellular communication and RNA stability in the extracellular environment.

Wan, J. Shi, M. Shi, Huang et al. report a role for lactate dehydrogenase B in regulating CD8⁺ T cell disulfidptosis and exhaustion through the activity of glucose-6-phosphate dehydrogenase, thereby impacting the efficacy of antitumour immunity.

Saur, Lesage et al. report that RNA:DNA hybrids arise at double-strand breaks in transcribed genes, independently of de novo recruitment of RNA polymerase II/III, as a result of DSB-induced transcriptional repression.

Xu, Meng, St-Germain et al. report that S1P in HDL induces a calcium signalling cascade involving E-Syt1 that ultimately promotes the formation of contact sites between the endoplasmic reticulum and the plasma membrane, as well as HDL-derived cholesterol transport.

Conway et al. show that integrin β1 phosphorylation is regulated through balanced activities of tyrosine kinases, such as Src and Arg, and phosphatases, such as PTP-PEST and Shp2, facilitating invadopodia formation and invasion of breast cancer cells.

Chen, Zhou, Xue et al. show that psychological stress leads to noradrenaline release and Alkbh5 downregulation, causing the transfer of extracellular vesicles containing m⁶A-modified RNAs to neurons to regulate innervation and pancreatic cancer development.

Arya et al. report that migrating neutrophils resolve acute inflammation by releasing exosomes associated with nuclear DNA. This process is distinct from the release of neutrophil extracellular traps, and relies on the lamin B receptor.

Hsu, Wang, Manne et al. identify ALDH4A1 as a component of the mitochondrial pyruvate carrier complex, which plays a non-canonical role in regulating pyruvate homeostasis in mitochondria, TCA cycle entry and tumour suppression.

Skowyra and Rapoport find that peroxisomal proteins with N-terminal PTS2 signals are imported through a nuclear pore-like conduit by PEX7 and a receptor. PEX7 then returns through the same conduit and is extracted into the cytosol by the chaperone PEX39.

Wei et al. report that MBD2 forms condensates through phase separation in diverse cancers where it assembles the NuRD complex. MBD2 condensates are redox-sensitive and mediate transcriptional repression in cancer cells.

Van Nerum et al. show that dimethyl α-ketoglutarate enhances the production and functional maturation of human trophectoderm-like cells from embryonic stem cells by regulating histone acetyltransferase activity and the pluripotency network.