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Receptor-mediated endocytosis delivers low-density lipoproteins (LDLs) to late endosomes, from where cholesterol is trafficked to mitochondria. Zhou et al. report that LDL-containing endosomes fuse with mitochondria, supplying cholesterol for steroid biosynthesis and enabling mitochondrial degradation of the LDL receptor.
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.
Chun-Yan Lim is a group leader at the Guangzhou Laboratory, China, studying organelle contacts as metabolic signaling hubs. We reached out to Chun-Yan to discuss his scientific career and life in the lab.
How mucosal-associated invariant T (MAIT) cells acquire memory-like features after infection and the factors that control this process have been unclear. A study now defines two subsets of antigen-adapted MAIT cells emerging after immunization that differ in functions, lung localization and metabolic requirements.
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.
Accumulation of senescent cells and compositional changes in gut microbiota have been independently reported to occur as a function of age. A study now suggests that these two seemingly disparate processes are more intimately linked than previously appreciated via a B cell–IgA–microbiota axis.
This study reveals that thermogenic stimuli activate mitochondrial proteolysis via LONP1 to sustain the succinate levels required for efficient conversion of white adipocytes to beige adipocytes. Our work highlights mitochondrial proteases (mitoproteases) as a link between environmental stimuli, metabolite levels and cell identity switching.
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.
Augsornworawat et al. perform single-nucleus multi-omics and integrated transcriptional and chromatin analysis to identify differences between human stem cell-derived and primary islets.
The loss of the polybromo-1 (PBRM1) subunit in a class of SWI/SNF chromatin remodelling complexes in clear cell renal cell carcinoma redirects the deficient complexes to aberrant enhancer regions. The catalytic subunit SMARCA4 of the PBRM1-deficient complexes recruits the nuclear factor-κB transcription factor to drive pro-tumorigenic programs.
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.
In cancer, alternative polyadenylation has been shown to lead to altered 3′ UTRs with different regulatory potentials. A study now suggests a mechanism that leads to 3′ UTR lengthening and translational repression of a subset of metastasis-suppressing genes, revealing a new prospective therapeutic vulnerability.
The selenoprotein glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, a form of cell death earmarked by unrestrained lipid peroxidation. A new study shows that the metabolic enzyme creatinine kinase B (CKB) phosphorylates GPX4, which may influence the susceptibility of cancer cells to ferroptosis.
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.