News & Views

When transcription by RNA polymerase II is stalled by ultraviolet-induced DNA damage, it recruits repair factors, leading to excision of the damaged site and DNA synthesis to fill the gap. Three new studies show that, for aldehyde-induced DNA crosslinks, repair is activated by the same factors, but without base excision and gap filling.

Organ morphogenesis begins with proliferation, which results in tissue pressures and site-specific YAP expression, nuclear translocation and signalling. A study now reports the involvement of anisotropy, localized pressure and YAP signalling in organizer-forming cascades, introducing a new chapter of molecular mechanobiology of organogenesis.

Eukaryotic transcriptional machinery often shows local enrichment in dynamic clusters at sites of high expression. A study of zebrafish embryos shows that such clusters can fine-tune the timing of zygotic genome activation by sequestering a component required for productive transcription, thus limiting its availability to other genes.

Diverse, specialized immune cells defend against pathogens and cancer cells. A new study reveals the comprehensive lipid compositions of these cells, with unique lipidomes associated with various immune cell types. They show that cell-specific lipid compositions determine a key functional phenotype: their susceptibility to ferroptosis.

Progeria, or premature ageing, is a devastating condition caused by defects in the nuclear envelope and is associated with systemic inflammation. A study now shows in animal models that inhibiting necroptosis, and particularly activity of the RIPK1 kinase, reduces inflammation and results in a meaningful extension in lifespan¹.

β-propeller protein-associated neurodegeneration (BPAN) is caused by loss of functional WIPI4. A new study reports that depletion of WIPI4 induces ferroptosis via changes in mitochondrial membrane lipids, independently of the role of WIPI4 in autophagy, providing insights into the cause of neurodegeneration in BPAN.

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.

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.

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.

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.

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.

Despite a growing understanding of the immunostimulatory properties of mitochondrial DNA (mtDNA), little is known about how and why mtDNA escapes its mitochondrial confines. A study now describes an endosomal trafficking pathway that facilitates mtDNA egress and provides an additional mechanism of mtDNA release in vitro.

How do metabolic stresses trigger catabolic autophagy for cell survival? A study now reveals that the metabolite sensor Pho81 integrates into and activates the kinase activity of the Atg1 complex for pexophagy triggered by phosphate starvation. This demonstrates the plasticity of the autophagy-initiating Atg1 complex.

Lipids have a pivotal role in the growth of oocytes and fertilized eggs. Ultra-sensitive lipidome analysis provides a complete overview of the lipid profile during early embryonic development and brings insights into how dynamic lipid remodelling determines the fate of mammalian embryos.

Cell–cell adhesions are inevitably exposed to mechanical forces. A landmark paper by Yonemura et al. identified how tension alters molecular function of the cadherin adhesion apparatus. Its legacy lies in the many on-going efforts to understand how mechanical force is used in cell–cell communication.

Extracellular vesicles carry proteins and lipids between cells. In a giant step forward for the field, a 2007 study published in Nature Cell Biology showed that secreted vesicles contain genetic material that is active within acceptor cells, reviving interest in extracellular vesicle-based communication in plant and animal biology.

Epithelial–mesenchymal transition (EMT) is crucial in embryogenesis and can be exploited by cancer cells to gain metastatic abilities. A hallmark of EMT is E-cadherin loss. In 2000, Snail was reported as the first E-cadherin repressor identified in the context of EMT, advancing our understanding of embryonic development and cancer progression.

Totipotency is the absence of any developmental restriction, a feature naturally found in the early embryo right after fertilization. Generating an in vitro totipotent stem cell model is not a trivial task. For this reason, a set of stringent criteria for the identification of bona fide totipotent stem cells have been proposed.

The interplay between DNA and its associated proteins has a crucial role in regulating gene expression and determining cellular identity. Here we revisit an earlier Nature Cell Biology study that established the chromatin signature associated with pluripotency.