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Liang et al. report mechanisms of migrasome biogenesis in migrating cells. They propose that sphingomyelin synthase 2 (SMS2) is required for migrasomes, first by localizing in stable puncta where they eventually form migrasome structures.
Hoetker et al. show that H3K36 methylation exerts a dual role in cell identity maintenance: it integrates TGFβ signals at mesenchymal targets to keep them active and prevents the activation of alternative lineage programmes via enhancer methylation.
Ghersi et al. report that haematopoietic stem and progenitor cell heterogeneity is established on the haemogenic endothelium level and is, at least in part, regulated by microRNA-128-mediated modulation of Wnt and Notch signalling.
Chen, Neil, Tan, Rudraraju et al. use an induced trophoblast stem-cell-based model of SARS-CoV-2 infection and identify syncytiotrophoblasts as the cells targeted by the virus in the early placenta.
Zhang, Jiang and colleagues demonstrate that, independent of its role in innate immunity, STING can target and inhibit HK2 activity, thereby blocking tumour aerobic glycolysis and enhancing antitumour immune responses.
Alkhoury et al. show that the class 3 phosphatidylinositol-3-kinase Vps15 subunit coactivates the circadian clock transcription factor Bmal1–Clock for metabolic rhythmicity in the liver and promotes pro-anabolic de novo purine synthesis.
Gaggioli, Lo et al. show that the histone methyltransferase EHMT2/G9a catalyses heterochromatin assembly at stressed replication forks. Untimely heterochromatin disassembly by demethylase KDM3A exposes forks to PRIMPOL-mediated genome instability.
Zhang, Xu, Liu, Wang et al. identify an inhibitory mechanism for RIPK1 kinase through EGLN1/pVHL-mediated proline hydroxylation, which is disrupted upon prolonged hypoxia that activates RIPK1 activity to promote cell death and inflammation.
Enkler et al. show that a pool of Arf1 at lipid droplets is implicated in mitochondrial ATP production control through regulation of fatty acid metabolism and acetyl-CoA transfer to mitochondria.
Gao, Mathur, Tam and colleagues characterize transcriptomic and epigenomic alterations at the maternal–fetal interface in patients with COVID-19, thereby providing insights into aberrant pregnancy outcomes associated with SARS-COV-2 infection.
Martinez-Lopez et al. show that fasting or lipid availability stimulates mTORC2 activity in the liver, leading to phosphorylation of NDRG1 and NDRG1–CDC42-mediated mitochondrial fission.
Through a genome-wide CRISPR synthetic viability screen for PARP-inhibitor resistance, Chen and Ge et al. show that transmembrane nuclease NUMEN directs double-stranded DNA break repair pathway choice at the nuclear periphery.
Yang, Zhao, Wang and colleagues identify and characterize a pyrimidine biosynthetic complex pyrimidinosome that is regulated by AMP-activated protein kinase and facilitates dihydroorotate dehydrogenase-mediated ferroptosis resistance, thereby regulating cancer cell proliferation and survival.
Bharathan et al. discover that the endoplasmic reticulum associates with keratin intermediate filaments and desmosomal cell–cell junctions, and that desmosomes and the keratin cytoskeleton regulate the distribution, dynamics and function of the endoplasmic reticulum network.
Zhou et al. describe an intracellular transport pathway of low-density lipoprotein (LDL)–LDL receptor from the plasma membrane that bypasses lysosomes and delivers cholesterol to mitochondria for steroidogenesis.
Han et al. identify the long non-coding RNA LIPTER as a key mediator of lipid droplet transport and metabolism in human cardiomyocytes. LIPTER overexpression mitigates cardiomyopathy and preserves cardiac function in obese and diabetic mouse models.
Choi et al. show that autophagy is activated in disease-associated microglia in Alzheimer’s disease mouse models, which prevents microglial senescence entry. Blocking microglial autophagy aggravates neuropathology in Alzheimer’s disease mice.
Riffelmacher et al. show that immunization with a live vaccine strain leads to the expansion of two memory-like mucosal-associated invariant T cell lineages with distinct metabolic needs, effector programmes and protective capacities.
Fu, Sun, Xue, Zhou et al. show that the mitoprotease LONP1 selectively degrades a complex II component to control intracellular succinate levels, which is needed for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling.
Kawamoto, Uemura et al. show that commensal bacteria induce senescence in gut germinal centre B cells, leading to changes in the immunoglobulin A antibodies that target gut bacteria and in the composition of gut microbiota in aged mice.