Reviews & Analysis

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.

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.

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.

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.

The cGAS–STING cytosolic double-stranded-DNA-sensing pathway provides protection against infection but also contributes to inflammatory pathology and thus must be tightly regulated. In this issue, Jie et al. find that endoplasmic-reticulum-associated degradation of the adaptor STING by SEL1L–HRD1 controls steady-state STING levels to limit STING-driven inflammation.

The SEL1L–HRD1 endoplasmic reticulum-associated degradation pathway negatively regulates STING-mediated innate immunity by ubiquitinating and targeting STING for proteasomal degradation, thereby limiting its activation.

The Mediterranean diet correlates with increased human lifespan; it is rich in foods with high levels of cis-monounsaturated fatty acids (MUFAs), such as olive oil. A study now shows that MUFAs stimulate a lipid droplet–peroxisome organelle network to decrease lipid oxidation and protect cell membranes during ageing.

Direct conversions offer an alternative approach to generate insulin-producing cells for cell therapy in diabetes. A study reports a method to convert human stomach-derived gastric stem cells into functional insulin-producing cells through a unique differentiation path.

Skin wounds induce an epigenetic memory that accelerates the healing of subsequent injuries. The underlying mechanism is now shown to involve epigenetic chromatin modifications in stem cells from a field of distal hair follicles that surround the injury. Importantly, this mechanism also results in a predisposition for skin cancer development.

Coordination of protein quality control processes across organelles is poorly understood. A study now shows that the cytosolic juxtanuclear quality control (JUNQ) and intranuclear quality control (INQ) compartments face each other on opposite sides of the nuclear envelope before their vacuolar degradation, promoting proteostasis.

The house-keeping aminoacyl-tRNA synthetases are increasingly recognized for their regulatory roles beyond protein synthesis. Research now uncovers a function of nuclear arginyl-tRNA synthetase in the regulation of alternative mRNA splicing through SRRM2 in response to inflammation and decreased arginine levels.

In adult Drosophila, the sense of touch is mediated by mechanosensory organs, namely tactile bristles in the epidermis. A new study reveals that a previously unknown type of epidermal cell, named the F-cell, is recruited to ensheath the tactile bristle and is required for touch sensing.

Acutely damaged lysosomes can regenerate themselves by repurposing damaged membranes. After damage, cytosolic TBC1D15 relocalizes to impaired lysosomes and assembles the autophagic lysosomal reformation machinery to drive this regeneration. This mechanism exemplifies an immediate cellular response to mitigate the crisis of severe lysosomal damage.

DNMT3A is best known for its de novo DNA methyltransferase activity. But a new study shows that the protein also has a role in RNA splicing during activation of embryonic and haematopoietic stem cells. This introduces a new perspective for approaching diseases associated with DNMT3A mutations.

Using single-cell transcriptomics and functional assays, we identified various subsets of pancreatic beta cells. One subset, characterized by high levels of CD63, demonstrated enhanced glucose metabolism, mitochondrial activity, and glucose-induced insulin secretion, and the proportion of these beta cells was decreased in mouse models of type 2 diabetes (T2D) and humans with T2D.

Biomolecular condensation of macromolecules is an increasingly important concept in cell biology. Indeed, research on condensates touches on multiple areas of research, from biochemistry to biophysics and from organelles to cell polarity. We asked experts at the forefront of this field to comment on what excites them most regarding biomolecular condensation, as well as on current challenges, priorities and needs for the functional study of condensates.

The molecular and cellular events that occur during the onset of human organogenesis remain mysterious. We used single-cell and spatial transcriptomics to provide a global view of human embryonic cell-type specification, shedding light on developmental processes such as axial patterning, stage transition, and differences between human and mouse embryonic development.

Programmed cell death (PCD) enables cells to co-ordinate their exit to benefit the surviving organism. A new study describes how cells can programme their death by inducing extensive disulfide bonding of the actin cytoskeleton in response to an imbalance of cystine, a raw material for glutathione production.