News & Views

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.

The regulatory mechanisms that drive oncogene expression in gliomas remain poorly understood. A study now identifies a role for widespread rearrangements of the enhancer connectome. Such rearrangements are linked to known genetic risk variants, revealing how genetic predisposition contributes to malignancy.

During wound healing, epithelial gaps trigger curvature-dependent ER remodelling. Tubules form at convex cell edges and promote lamellipodial crawling, whereas ER sheets at concave edges support purse-string contractions. Cytoskeletal forces drive this reorganization and position the ER as a key mechanotransducer in tissue repair.

Glioblastoma (GBM) heterogeneity might arise because of the activation of various gene core regulatory circuitries (CRCs). A new study highlights the central role of HOXB3 in GBM CRCs and how peptide-mediated perturbation of HOXB3-related CRCs in GBM holds potential as treatment for a subset of patients.

The transition of a pluripotent stem cell into a differentiated lineage is one of the most complex yet precisely orchestrated events in developmental biology. A study now reveals that mechanical and osmotic forces, long considered background players in guiding this transition, are essential regulators of chromatin accessibility and cell fate decisions.

ATM inhibitors (ATMi) cause cell death by enabling CtIP to induce excessive DNA resection. A study now shows that ERCC6L2 regulates resection by forming condensates with CtIP to prevent its degradation. Loss of ERCC6L2 decreases sensitivity to ATMi, which suggests that ERCC6L2 deficiency can be a biomarker for ATMi resistance.

The AMP-dependent protein kinase AMPK is thought to be activated only when cellular energy levels are low. However, a study now finds that intracellular AMP is generated from extracellular adenosine in an intricate growth signalling cascade, explaining how AMPK can be regulated by extracellular cues.

A study now indicates that CD160⁺CD8⁺ T cells in patients with colorectal cancer modulate anti-tumour immune responses and may influence disease progression. Their combination with immune checkpoint blockade therapy has emerged as a promising strategy to enhance therapeutic efficacy and patient outcomes in colorectal cancer.

During development as cells exit a pluripotent state, chromatin looping interactions are strengthened, but the mechanism for this is unknown. A study now shows that CTCF–RBP interactions increase upon differentiation of embryonic stem cells to neural stem cells, and that the non-coding RNA Pantr1 collaborates with CTCF and RBPs to contract the genome.