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PLOS Biology: New Articles

  • The transcription factor SKN-1 drives lysosomal enlargement during aging to maintain function

    by Xinyu Wang, Huimin Liu, Xiaoman Wang, Ben Zhou, Haiqing Tang, Shanshan Pang

    Lysosomes are critical hubs for both cellular degradation and signal transduction, yet their function declines with age. Aging is also associated with significant changes in lysosomal morphology, but the physiological significance of these alterations remains poorly understood. Here, we find that a subset of aged lysosomes undergo enlargement resulting from lysosomal dysfunction in C. elegans. Importantly, this enlargement is not merely a passive consequence of functional decline but represents an active adaptive response to preserve lysosomal degradation capacity. Blocking lysosomal enlargement exacerbates the impaired degradation of dysfunctional lysosomes. Mechanistically, lysosomal enlargement is a transcriptionally regulated process governed by the longevity transcription factor SKN-1, which responds to lysosomal dysfunction by restricting fission and thereby induces lysosomal enlargement. Furthermore, in long-lived germline-deficient animals, SKN-1 activation induces lysosomal enlargement, thereby promoting lysosomal degradation and contributing to longevity. These findings unveil a morphological adaptation that safeguards lysosomal homeostasis, with potential relevance for lysosomal aging and life span.

  • Adaptive communication between cell assemblies and “reader” neurons shapes flexible brain dynamics

    by Marco N. Pompili, Ralitsa Todorova, Céline J. Boucly, Eulalie M. Leroux, Sidney I. Wiener, Michaël Zugaro

    Cell assemblies are considered fundamental units of brain activity, underlying diverse functions ranging from perception to memory and decision-making. Cell assemblies have generally been studied in relation to specific stimuli or actions, but this approach does not readily extend to more abstract constructs. An alternative approach is to assess cell assemblies without making reference to external variables, and instead focus on internal brain processes—by assessing assemblies by their endogenous ability to effectively elicit specific responses in downstream (“reader”) neurons. However, this compelling idea currently lacks experimental support. Here, we provide evidence for assembly–reader communication. Large-scale cross-structural recordings in rats revealed that reader activation was genuinely collective, functionally selective, yet flexible, implementing both pattern separation and completion. These processes occurred at the time scale of membrane integration, synaptic plasticity, and gamma oscillations. Finally, assembly–reader couplings were selectively modified upon associative learning, indicating that they were plastic and could become bound to behaviorally relevant variables. These results support cell assemblies as an endogenous mechanism for brain function.

  • Correction: Catecholamines reduce choice history biases in perceptual decision making

    by Jan Willem de Gee, Niels A. Kloosterman, Anke Braun, Tobias H Donner



  • Control of mitochondrial dynamics by the metabolic regulator dPGC1 limits Yorkie-induced oncogenic growth in Drosophila

    by Wei Qi Guinevere Sew, Maria Molano-Fernández, Zhiquan Li, Artim Lange, Nahia Pérez de Ciriza, Lene Juel Rasmussen, Hector Herranz

    Mitochondrial function and dynamics are essential for maintaining cellular homeostasis and overall health. Disruptions in these processes can contribute to various diseases, including cancer. The Hippo signaling pathway, a key regulator of tissue growth, plays a central role in cancer through its main effector, the Yes-associated protein (YAP), known as Yorkie (Yki) in Drosophila. In this model organism, Yki upregulation drives benign tissue overgrowth in imaginal discs. Our research demonstrates that the conserved metabolic regulator dPGC1 restricts Yki-driven tissue hyperplasia and helps maintain epithelial integrity in vivo. Combined Yki upregulation and dPGC1 depletion results in tumors characterized by enlarged mitochondria and the upregulation of genes promoting mitochondrial fusion, a condition that is both necessary and sufficient for Yki-driven oncogenic growth. We further demonstrate that mitochondrial enlargement is associated with increased levels of the cell cycle regulator Cyclin E, which plays a critical role in tumor development. These findings identify dPGC1 as a context-dependent tumor suppressor that coordinates mitochondrial dynamics and cell cycle regulation in response to oncogene activation, with implications for understanding cancer development in humans.

  • How to integrate patient and carer perspectives, methodological rigor, and ethics into biomedical research funding

    by Hella Lichtenberg, Christina Müller, Henk Lindeman, Leila Ali, Anja Minheere, Monique van den Eijnden, Ulrich Dirnagl

    Patient and carer perspectives, methodological rigor, and ethical considerations can all be successfully integrated into the biomedical funding process. Drawing on experiences with ERA-NET NEURON, we present a structured, scalable, and transferable model for funders to follow. Patient and carer perspectives, methodological rigor and ethical considerations can all be successfully integrated into the biomedical funding process. This Community Page draws on experiences with ERA-NET NEURON to present a structured, scalable and transferable model for funders to follow.