ER-associated sorting links proteostasis to photosynthesis

Proteotoxic stress challenges multiple organelles, but how plants coordinate proteasome capacity with organellar function remains unclear. Langin et al. reveal that endoplasmic reticulum (ER)-associated sorting of NAC53/78 toggles these transcription factors between ER-associated degradation and nuclear activation, coupling proteasome induction to repression of photosynthesis-associated genes during stress.

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Horizontal mitochondrial transfer: an emerging field in cell biology

The field of horizontal mitochondrial transfer (HMT), also referred to as intercellular mitochondrial transfer, has recently gained momentum due to an increasing number of publications that go well beyond diseases such as cancer. From co-culture experiments to in vivo evidence in mouse cancer models, noncancerous diseases, and normal tissue and organ homeostasis and development, it is becoming increasingly clear that HMT is a fundamental physiological phenomenon broadly relevant to complex organisms. Recent methodological advances, epitomized by ultra-high-resolution microscopy and spatial and single-cell multiomics technologies, allow for research that strongly supports HMT as an emerging area of cell biology.

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Lamin-ating the genome: quantitative gatekeeping of replication initiation

Discovered in the 1970s, nuclear lamins control chromatin organization and are linked to many diseases. Zhang et al. now find that lamin A/C quantitatively constrains DNA replication initiation by limiting chromatin accessibility and sequestering proliferating cell nuclear antigen, extending lamin’s long-known role in replication to the control of origin firing.

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A temporal framework for error-free mitosis

The spindle assembly checkpoint (SAC) promotes mitotic fidelity by delaying anaphase until all kinetochores are stably attached to spindle microtubules. SAC silencing is increasingly recognised as a dynamic, sensitive process involving multiple molecular events at individual kinetochores. In Cell Reports, Conway et al. reveal how these events sequentially unfold.

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Remaking an exit: dynamic regulation of ER exit sites by post-translational modifications

Endoplasmic reticulum exit sites (ERES) are dynamic platforms that coordinate not only protein trafficking but also protein quality control and signaling functions. ERES size, composition, architecture, interactions, and activity must be precisely remodeled in response to myriad pathophysiological cues to finely tune cellular homeostasis. However, the molecular mechanisms underlying this regulation remain incompletely understood. Coat protein complex II (COPII) mediates many ERES functions, and its subunits and client cargos are subject to spatiotemporal regulation by post-translational modifications (PTMs) that modulate ERES assembly, cargo selection, and inter-organelle communication. In this article, we review recent advances in understanding how PTMs control the organization and functional versatility of ERES and the COPII system.

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How cohesin navigates homologous recombination

Homologous recombination repairs DNA double-strand breaks by copying genetic information from an intact DNA template, but how the homologous sequence is located within the vast 3D genome remains unclear. In this forum, we discuss how cohesin, a key chromatin organizer, guides the homology search during DNA repair in mammalian cells.

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Sneaking in the enemy: infected macrophages permeabilize the endothelium

The endothelial barrier provides a defense against bacterial pathogens. Muenkel et al. show that endothelial barrier function increases when macrophages interact with endothelial cells. Conversely, infected macrophages decrease endothelial barrier function and transmigrate more efficiently. These findings show that the endothelium is biomechanically responsive to the infection status of macrophages.

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Nuclear CGAS promotes cancer dissemination

Nuclear CGAS has previously been shown to promote tumor progression by inhibiting DNA repair. Recent data from Zhang et al. demonstrate that, upon phosphorylation by PKCα, CGAS translocates to the nucleus and initiates a CTNNB1-dependent program supporting metastatic dissemination. Thus, nuclear CGAS emerges as a multifaceted driver of cancer progression.

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Vitamins tune cell death thresholds

Vitamins are essential micronutrients traditionally viewed as passive cofactors that sustain cellular homeostasis. Emerging evidence challenges this notion, identifying vitamins as active regulators of cell fate that tune the threshold for regulated cell death. Through coordinated control of redox balance, metabolic pathways, and signaling networks, vitamins shape cellular susceptibility to diverse death programs. Their effects are highly context-dependent, enabling both prosurvival and prodeath outcomes depending on dose, cell type, and metabolic state. Recent studies further uncover noncanonical mechanisms linking vitamins to lipid remodeling, membrane trafficking, and organelle integrity. Collectively, these advances establish vitamins as dynamic modulators of cellular vulnerability and highlight their potential as therapeutic targets for selectively manipulating cell death in disease.

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A splicing switch enables SR45a-driven thermotolerance in plants

Heat stress reshapes plant transcriptomes through alternative splicing, yet the regulatory logic governing isoform switching remains poorly understood. Recently, a heat-activated, branch-point-dependent splicing switch in Serine/arginine-rich splicing factor 45a (SR45a) was uncovered by Xu et al. This switch couples transcriptional activation to isoform remodeling, driving thermotolerance.

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Microtubule function in pluripotent mouse embryonic stem cells

Cultured mouse embryonic stem cells can be maintained in a naïve pluripotent state, meaning the cells can give rise to all lineages of the embryo proper while self-renewing through rapid proliferation. This review summarizes recent advances in our understanding of the role of the microtubule (MT) cytoskeleton in pluripotency maintenance. We focus on intercellular bridge MTs, as these are prominent, long-lasting structures that arise during cytokinesis yet maintain the connection between dividing sister cells into the next cell cycle. We describe how MT stability sets cytokinesis duration and how this may influence pluripotency maintenance, division symmetry, midbody inheritance, and abscission. Together, these findings highlight an emerging paradigm: MTs are not merely structural scaffolds but active players in stem cell maintenance.

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RBPs tune Notch signalling to shape neural fate

Maintaining the proper balance between stem cell self-renewal and differentiated progeny production is essential for tissue development. Li et al. (2026) uncover a novel post-transcriptional mechanism that fine-tunes Notch signalling in Drosophila neural progenitors to preserve this balance, expanding the growing repertoire of RNA-binding proteins implicated in neural lineage progression.

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Cellular lipid imaging at the ultrastructural level

Lipids are fundamental organizers of biological membranes, yet visualizing lipid species within subcellular organelles has remained beyond experimental reach. Lennartz et al. introduce Lipid-correlative light and electron microscopy (CLEM), a CLEM workflow that maps lipid species onto membrane ultrastructure with nanoscale precision, uncovering active sphingomyelin sorting within the early endosome.

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Lysosomes join the circular RNA decay machinery

Circular RNAs (circRNAs) are covalently closed, stable RNA molecules with broad physiological functions. Precise regulation of circRNA turnover is essential for cellular homeostasis. A recent study by Deng et al. uncovers an evolutionarily conserved mechanism in which RNAseK and the lysosome act synergistically to degrade circRNAs across metazoans.

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Immune cell lncRNAs reprogram the tumor microenvironment

Long noncoding RNAs (lncRNAs) regulate the tumor microenvironment (TME), yet their cell-intrinsic roles within immune populations of the TME remain underappreciated. In this review, we shift focus from the cancer cell to the immune compartment, systematically reviewing how immune cell-intrinsic lncRNAs govern CD8+ T cell exhaustion, CD4+ T cell polarization, NK cell cytotoxicity, dendritic cell antigen presentation, and macrophage inflammatory programming. We highlight lncRNAs that function as molecular switches—tipping immune cells between antitumor effector and immunosuppressive states—and examine how exosomal lncRNAs extend these regulatory circuits across cellular boundaries within the TME. Finally, we evaluate opportunities for lncRNA-based biomarkers and therapies designed to target the immune landscape, outlining a framework for integrating immune-intrinsic lncRNA biology into precision immuno-oncology.

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Nascent peptides emerge as regulators of mRNA stability

Mobile genetic elements and their hosts engage in continuous evolutionary conflict. Marino et al. recently uncovered an unusual anti-CRISPR mechanism: the phage protein AcrVA2 triggers translation-coupled mRNA degradation by recognizing nascent Cas12. The findings suggest that nascent peptides may signal an underappreciated layer of gene regulation across the kingdoms of life.

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Ruptoblasts: Explosive cytotoxicity from an ancient lineage

Cytotoxic immunity has long seemed the exclusive province of blood. Chai et al. challenge this view by describing ruptoblasts, glandular cells that explode on hormonal cues to kill neighbors across kingdoms. Ruptosis, their distinctive form of death, hints at an ancient immune logic that mainstream model organisms appear to have quietly lost.

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Primed to squeeze: mechanical memory in confined migration

Do cells remember past mechanical experiences to prepare for future physical challenges? Holle et al. demonstrate that stiffness priming enhances confined migration through NFATC2-dependent programs. Beyond this specific mechanism, their work supports the emerging concept of mechanical memory as a hierarchy of interconnected cellular states operating across multiple timescales.

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The octameric shift in plant immune signaling

Nucleotide-binding leucine-rich repeat (NLR) receptors are ubiquitous intracellular sensors. Guo et al. recently revealed that the wheat CCG10-NLR, Wheat Autoimmunity 3, forms a previously undescribed plant octameric resistosome to mediate cell death and immunity. This discovery uncovers a distinct configuration, highlighting the remarkable structural plasticity in plant immune signaling.

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Horizontal transfer of mitochondria in cancer: The physiology reborn in disease?

Intercellular mitochondria transfer has emerged as a new form of cell-to-cell communication with profound consequences for cellular fate. A growing body of evidence defines mitochondria transfer between cells as a new pathological program in which cancer cells appropriate functional mitochondria from donor cells, thereby co-opting conserved physiological mechanisms of energy allocation to gain bioenergetic and phenotypic advantages. Our recent work demonstrates the prevalence of mitochondria transfer at the nerve–cancer interface, with neurons, though not exclusively, serving as a prominent source of the organelle. This suggests an unrecognized role of the nervous system in systemic energy redistribution and indicates that tumors may exploit this ancient, physiologically grounded mechanism to fuel progression and metastasis.

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Spindle errors: A stress test for epithelial robustness

Bosveld et al. uncover how epithelial tissue buffers mitotic spindle errors. In the Drosophila notum, cells displaced by spindle misorientation either reintegrate via cell-autonomous and nonautonomous forces or are eliminated. This coordinated response links cell and tissue mechanics, Hippo-dependent survival signaling, and systemic tumor necrosis factor signaling-mediated apoptosis to maintain epithelial homeostasis.

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Multicellular ecosystems: Linking cellular diversity to tissue function and disease

Tissue function emerges from coordinated interactions among diverse cell populations, whereas disruption of these interactions can lead to dysfunction. Recent advances in single-cell and spatial genomics have not only cataloged cellular diversity but also revealed how tissues are organized as dynamic multicellular ecosystems. Moving beyond descriptive cell atlases toward functional, system-level representations represents a major frontier in tissue biology. In this review, we outline conceptual and methodological frameworks for dissecting multicellular coordination, highlight recurrent multicellular ecosystems across physiological and pathological contexts, and explore translational opportunities such as patient stratification, therapeutic reprogramming, and regenerative strategies. Viewing tissues through an ecosystem lens provides a unifying framework that links cellular diversity to emergent tissue function and informs strategies for disease intervention.

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Orchestrating the signaling-bias at the protease-activated receptor, PAR1

The protease-activated receptor-1 (PAR1) exhibits biased agonism upon activation by the coagulant protease thrombin and the anticoagulant protease activated protein C. In a recent study, Gonzalez Ramirez et al. demonstrate that differences in receptor conformations, engagement of G protein-coupled receptor kinase 5, and receptor phosphorylation patterns govern the biased agonism at PAR1.

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Crashing by design: Utilizing DNA damage for MCC differentiation

Multiciliated cells (MCCs) represent a complex cell type with a range of unique features. Jewett et al. identify a novel DNA damage response (DDR) that occurs during MCC differentiation. Inhibition of DDR blocks the formation of MCCs, indicating that this damage response is likely an important step in MCC differentiation.

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The value of a shared lab: Our insights

Tackling scientific questions benefits from different points of view. Coleading a lab by two scientists may stimulate scientific discussion while also providing a different form of mentorship. Here, we share our experience in running a joint lab and discuss how this form of dual leadership contributes to collaborative science.

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Atypical membrane fusion uncovered by a noncanonical mechanism

The bacterial-like identity of membranes in modern eukaryotes and the formation and disassembly of large hemifusion diaphragms during organelle fusion, remain unresolved problems in cell biology. In this forum, we comment on a noncanonical fusion pathway, supported by molecular simulations, which offers a unified physicochemical framework to rationalize these phenomena.

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The astrocytic connectome: Gap-Junction topology beyond diffuse syncytium

Whether astrocytes form selective long-range networks remains unresolved. Cooper et al. use connexin 43-TurboID to reveal region-specific, plastic astrocyte gap-junction networks that partly overlap yet are not reducible to canonical neuronal projections. We discuss how this work refines the concept of astrocyte syncytial coupling and expands models of inter-regional brain connectivity.

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Bridging oxidative post-translational modifications to biological meaning

Reactive oxygen species (ROS) function as both damaging and signaling molecules by modifying macromolecules. Advances in proteomics have greatly expanded the identification of ROS target proteins, demonstrating redox modifications as a dominant form of post-translational regulation. However, determining which of these modifications are regulatory and impact protein function remains a key challenge in the field. In this opinion article, we discuss the promise and peril of prioritizing ROS targets identified by proteomics solely based on the highest levels of oxidation for downstream scrutiny. We argue for the integration of functional genomics as a systematic and orthogonal approach for connecting redox-based protein modifications with functional outcomes. This combined approach accelerates the discovery of novel ROS- and other metabolite-modified signaling pathways.

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Telomere heterochromatin-mediated compartmentalization: Where ALT begins

Alternative lengthening of telomeres (ALT) is a recombination-mediated telomere maintenance mechanism. Although the core ALT machinery is defined, the initiating events remain unresolved. Taylor et al. demonstrate that telomeric heterochromatin enrichment drives nuclear compartmentalization, promyelocytic leukemia body nucleation, and telomere clustering, establishing a chromatin-defined environment that is permissive for recombination.

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