Articles in 2024

Weatherbee, Weberling, Gantner et al. find contrasting requirements for BMP in the anterior signalling centre and pre-implantation epiblast between mice and humans. They further find that NOTCH may be indispensable for human epiblast survival.

The tumour microenvironment produces nutrients that propel cancer development. New work finds that pancreatic ductal adenocarcinoma cells use one such nutrient, acetate, to alter protein acetylation, rerouting polyamine metabolism and promoting cell growth under acidosis—a finding with potential implications for treating this cancer.

The endoplasmic reticulum (ER) controls the synthesis of lipids and proteins and Ca²⁺ homeostasis, as well as contacting other organelles and the plasma membrane. A study now looks at a process by which this compartment is remodelled in axons during neurogenesis: the lysosomal clearance of ER subdomains, driven by FAM134 and CCPG1 proteins.

In this Perspective, Zhang discusses the latest advances in understanding of iron function, regulation and metabolism, as well as the implications for ferroptosis in health and disease.

Murthy et al. demonstrate that cancer-associated fibroblast-derived acetate regulates polyamine homeostasis via an ACSS2–SP1–SAT1 axis in pancreatic cancer cells, thus enabling cell survival and tumour development under acidosis.

Hoyer et al. establish that selective autophagy mechanisms are needed to remodel the ER and its proteome during in vitro neurogenesis across neuronal subcompartments and decode the substrate selectivity of ER-phagy receptors.

Biomolecular condensates are recognized for their ability to compartmentalize the cytoplasm without bounding membranes, but the degree to which they organize the cytoplasm has not been clear. A new study reveals that condensates at a scale of 100 nm are responsible for the organization of at least 18% of the cytoplasmic proteome.

Keber et al. use filtration chromatography and quantitative proteomics of Xenopus egg extracts and show that at least 18% of cytoplasmic proteins are organized in small ~100-nm biomolecular condensates.

Rai et al. report that CAMSAPs can bind to minus ends of microtubules attached to γ-tubulin ring complex (γ-TuRC) and drive microtubule release. They show that CDK5RAP2, but not CLASP2, inhibits CAMSAP-mediated microtubule release from γ-TuRC.

In this Review, Dai, Stockwell, Kroemer, Tang and colleagues offer a comprehensive discussion of the molecular regulation of ferroptosis and highlight how this may be potentially leveraged for therapeutic benefit for disease treatment.

Activation of innate immunity has been linked to the progression of type 1 diabetes. A study now shows that overexpression of METTL3, a writer protein of the m⁶A machinery that modifies mRNA, restrains interferon-stimulated genes when expressed in pancreatic β-cells, identifying it as a promising therapeutic target.

De Jesus et al. describe the redox-mediated regulation of m⁶A writer methyltransferase 3, which blunts innate immune responses by modification of RNA sensor and editor component mRNAs during the onset of type 1 diabetes in β-cells.

Scientists must actively advocate for infrastructure development and funding of emerging research directions through collective efforts. In India, this has been crucial to help reverse the brain drain and enable equitable contributions to research and development at the global level.

Contractile activity of both the epithelium and underlying mesenchyme are required for epithelial deformation and cell fate acquisition during early mouse hair follicle development. Subsequently, localized basement membrane remodelling facilitates the release of tension-generated pressure to promote cell divisions, tissue fluidification and downgrowth of the developing hair follicle.

The chemoresistant and immunoevasive characteristics of leukaemia stem cells (LSCs) impede the treatment efficacy for acute myeloid leukaemia (AML). We find that inhibiting the tyrosine phosphatase SHP-1 effectively alters the metabolic state of LSCs, making them more susceptible to chemotherapy and immune surveillance in AML.

Mechanical forces are ubiquitously present in biology. In recent years, it has become clear how plasma membranes detect these forces — but how do intracellular organelles such as lysosomes do the same, and what might be the functions of such intracellular mechanosensing? Answers may come through a report of a lysosomal mechanosensitive ion channel, TMEM63.

Li, Guo, Wang and colleagues show that the ion channels TMEM63 in Drosophila and TMEM63A in mouse mediate lysosomal mechanosensitivity and modulate lysosomal morphology and function.

As a major microenvironmental component in B cell lymphomas, T cells are highly relevant for current immunotherapeutic treatment strategies of such tumours. A study now provides an unprecedented multimodal insight into the composition and features of T cell subsets of the four main types of nodal B cell non-Hodgkin lymphoma.