News & Views

A study establishes a correlative light and electron microscopy workflow that reveals how individual lipid species distribute across nanoscale membrane domains, uncovering sphingomyelin sorting within the early endosome.

Tumour location dictates ferroptosis resistance. A study indicates that peritumoural adipose tissue aids tumours in evading ferroptosis by supplying tryptophan metabolites, including kynurenine and 3-hydroxykynurenine, which block NCOA4-mediated ferritinophagy to lower levels of labile iron and suppress lipid peroxidation.

Tumour acidosis is known to drive metabolic adaptations in cancer cells, contributing to their survival and resistance to therapies. A study now identifies a chondroitin sulfate-enriched glycocalyx as a key feature of the acidic tumour microenvironment in glioblastoma that limits lipid uptake and protects cells against death by ferroptosis.

Complexes of dynein, dynactin and adaptor drive retrograde trafficking, but how the complexes respond to load is unclear. A study now shows that mechanical load drives dynein–dynactin–adaptor complexes to assemble with three dyneins instead of two, which increases force production and suggests dynein can dynamically tune force output to meet specific cargo needs.

A new study shows that Whi3 condensates in Ashbya gossypii locally regulate translation of specific mRNAs, creating spatial biases in protein synthesis that co-ordinate multinucleate cell growth. Condensate size, RNA identity and protein biophysical properties tune translation outcomes, linking local translation with cell-scale growth dynamics.

Glucosylceramide accumulation — a hallmark of GBA1- and LRRK2-linked Parkinson’s disease — drives ectosome shedding from neurons. A study now shows that these plasma membrane-derived vesicles shuttle pathogenic α-synuclein across cells, revealing ectosomes as an underappreciated route of pathology propagation in Parkinson’s disease.

Research shows that the function of intrinsically disordered regions within proteins relies on both linear sequence motifs and broader chemical context, allowing evolution to preserve function without strict sequence conservation. Motifs and contextual chemistry jointly determine activity, with chemistry able to compensate for a loss of motifs.

The endoplasmic reticulum (ER) is central to protein synthesis, folding and secretion. A study now shows that ageing is characterized by a striking loss of ER mass and remodelling of the ER structure. This shift is driven by tissue-specific ER-phagy, and may contribute to age-related loss of proteostasis.

A newly discovered acidic nanolayer that envelopes lysosomes reveals that proton gradients extend beyond the organelle lumen, identifying a nanoscale regulatory interface that links luminal pH, TMEM175-mediated proton efflux, organelle positioning and neurodegeneration.

Damaged mitochondria must be removed to preserve organelle function, and a quality control pathway segregates damaged peripheral subdomains into small MTFP1-enriched mitochondria targeted for degradation. A study now identifies MISO as the key factor that promotes subdomain formation and links mitochondrial dynamics, quality control and mtDNA homeostasis.

Spatial organization of the tumour microenvironment is instrumental for tumour progression or sensitivity to therapies. A new study reveals that tumour-associated highly glycolytic SLC2A1⁺ macrophages create metabolic borders that limit cytotoxic T cells and immunotherapeutic responses in lung cancer, providing a ‘metabolic–spatial’ framework for overcoming resistance to checkpoint blockade.

Lactate acts as a metabolic fuel, a signalling molecule and a protein modifier. A study reveals that in glioblastoma, a lactate-mediated metabolic crosstalk between tumour-associated macrophages and glioblastoma stem-like cells enhances DNA repair, promotes stemness, drives immune evasion and accelerates tumour growth.

The discovery that CD8⁺ T cells divide asymmetrically has generated considerable speculation regarding how such divisions regulate the fate of these cells. Excitingly, a recent study links the inheritance of a fate determinant to divergence in CD8⁺ T cell fate among the daughters of an asymmetric division.

Chromosomes unfold and refold each time cells divide. A study by Schooley et al. demonstrates that chromosome-intrinsic and cytoplasmic factors uniquely contribute to interphase chromosome structure, with new possibilities for how gene expression programs are passed from mother cells to daughter cells.

Macrophages can either engulf targets whole (phagocytosis) or nibble them in small fragments (trogocytosis). Work now shows that this decision is controlled by cortical tension in the targets: low tension favours trogocytosis, whereas higher tension favours phagocytosis. These findings offer a new mechanical lens on immune recognition.

FSP1 is a key suppressor of lipid peroxidation and ferroptosis, yet it is largely dispensable in standard cell culture models. Two new studies now show that FSP1 becomes essential for tumour growth in vivo, establishing it as a context-specific cancer vulnerability and highlighting the therapeutic potential of FSP1 inhibition.

Targeting oncogenic KRAS holds great promise but is often limited by rapid adaptive resistance. A study now shows that RASH3D19 is regulated by microRNAs and promotes resistance to RAS inhibition by enhancing EGFR dimerization. Targeting RASH3D19 improves sensitivity to RAS inhibitors in preclinical settings.

A longstanding challenge in the biology of extracellular vesicles has been to define their core protein and lipid composition in human plasma. A new study addresses this limitation by applying high-throughput multi-omics to establish a molecular blueprint of circulating extracellular vesicles, providing robust markers for translational applications.

Haematopoietic stem cells (HSCs) are used in a variety of cellular therapies, but our ability to support these cells ex vivo remains technically challenging. A new study discovers that inhibiting ferroptosis promotes HSC expansion ex vivo and applies these findings to HSC transplant and gene editing approaches.

Phase separation is a mechanism for non-organellar macromolecule segregation typical in the cell cytosol and nucleus. Two recent studies revealed functional phase separation within the endoplasmic reticulum, where calcium-mediated condensates co-ordinate chaperones and disulfide catalysts to enhance secretory protein production.