Articles

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.

Using ribosome profiling, Navickas et al. show that heterogeneous nuclear ribonucleoprotein C functions with PABPC4 to regulate alternative polyadenylation of a set of mRNAs, which inhibits lung metastasis in xenograft models of breast cancer.

Wu et al. show that, upon activation by insulin-like growth factor 1 receptor and AKT, creatine kinase B exhibits a moonlighting function as protein kinase to phosphorylate glutathione peroxidase 4 to prevent its degradation, thereby suppressing ferroptosis and enhancing tumour growth in mice.

Ji et al. report that under basal conditions the SEL1L–HRD1 complex for endoplasmic reticulum-associated degradation ubiquitinates and negatively regulates STING protein levels in the endoplasmic reticulum, hence its activation.

Meng et al. report that lymphoid fate is programmed epigenetically rather than transcriptionally in haematopoietic stem cells and shed light on how epigenetic programming generates platelet differentiation pathways with distinct kinetics.

Papsdorf et al. show that mono-unsaturated fatty acids extend lifespan of C. elegans through induction of peroxisomes and lipid droplets in fat tissues and of a lipid signature predictive of decreased lipid oxidation.

Carbognin et al. report that ESRRB drives activation of the transcriptional programme regulating the formative transition of naive embryonic stem cells.

Yao et al. observe and characterize genomic redistribution of the PBAF complexes upon PBRM1 loss, leading to sustained RELA occupancy by SMARCA4, activation of the NF-kB pathway and enhanced kidney tumourigenesis.

Levra Levron et al. report that epidermal injury elicits the priming of distant memory progenitors that have not contributed in the original healing, but acquire enhanced repair abilities, although favouring field cancerization.

Sontag et al. show that nuclear misfolded proteins and juxtanuclear cytoplasmic misfolded proteins converge to opposite sides of the nuclear envelope, proximal to nuclear–vacuolar junctions for ESCRT-dependent egress to the vacuole.

Cui et al. find that arginine depletion and inflammation reduces nuclear localization of arginyl-tRNA synthetase, which influences alternative splicing via condensate-like serine/arginine repetitive matrix protein 2, and regulates cellular metabolism and response to inflammation.

Yan et al. harness genome-wide CRISPR screens and identify ILF3 as a signalling intermediate negatively regulating mTORC1 activation upon amino acid sensing. ILF3 recruits GATOR2 to tether the GATOR complexes to lysosomes and regulate mTORC1 activity.

Bhattacharya et al. describe a TFEB-independent lysosome membrane regeneration pathway that depends on TBC1D15, which stabilizes autophagic lysosomal reformation proteins, potentiating the formation of lysosomal tubules and dynamin-2-dependent scission.

Ramabadran et al. identify a DNA methylation-independent role for DNMT3A in stem cell activation, mediated through recruitment of SF3B1 and splicing regulation.

Weigert et al. show that an antagonistic relationship between DNA methyltransferase and Polycomb activity is globally responsible for the maintenance of intermediate methylation levels observed in trophoblast stem cells.