Biology subjects

Galeone, A.

Publications and source records attributed to Galeone, A..

5 recordsLinked to original sources

bioRxiv2026

Integrated cellular and molecular responses to uranium chemotoxicity in the metal-tolerant microalga Coelastrella sp. PCV

Understanding the toxicity of hazardous metals in microalgae is critical for environmental risk assessment and sustainable phycoremediation. Metal-tolerant organisms provide powerful models for dissecting the mechanisms that mitigate metal toxicity. Here, we investigated the cellular and molecular responses to uranium (U) chemotoxicity in the metal-tolerant microalga Coelastrella sp. PCV. We used an integrated multi-omics and high-resolution imaging approach, combined with physiological analyses, to elucidate the mechanisms underlying U tolerance in Coelastrella. Using TEM-EDX, U was localized to the cell wall, polyphosphate bodies within acidocalcisomes, and vacuoles. Three-dimensional cell reconstruction and morphometric analysis using FIB-SEM showed that U-challenged cells displayed increased vacuolization, reflecting sequestration of uranyl ions and autophagy-mediated detoxification. Transcriptome responses were rapid and extensive, characterized by repression of cell division and photosynthesis, and pronounced imbalance in protein turnover and trafficking. Uranium also disrupted the homeostasis of essential elements, with marked rewiring of gene networks governing molybdenum, manganese, phosphate, iron and calcium homeostasis, notably affecting transporters and metal-binding proteins. Coelastrella sp. PCV efficiently sequestered U in acidocalcisomes and vacuoles, while rapidly excluding U from the cell. These coordinated detoxification responses are likely mediated by calcium, iron, ABC, and MATE transporters among the strongly deregulated genes under U stress.

plant biology↗

bioRxiv2025

Mesodermal-specific MECP2 expression in Drosophila induces visceral and skeletal muscle defects rescued by butyrate supplementation

BackgroundPatients affected by Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) experience disabling muscle weakness and gastrointestinal dysmotility of unclear origin. Whether these defects arise cell-autonomously, rather than secondarily to neural dysfunction, and which developmental windows are most vulnerable to MeCP2 disfunction remains unresolved. MeCP2 is a dosage-sensitive transcriptional regulator, whose functions are tightly linked to chromatin states. Because short-chain fatty acids (SCFAs) are known to inhibit histone deacetylases (HDACs), a tractable in vivo model is needed to test the effect of HDAC modulation on muscle defects. MethodsWe misexpressed human MECP2 in the Drosophila melanogaster mesoderm that gives rise to skeletal and visceral muscles. We analyzed quantitatively their morphology and function. To assess the effects of SCFA supplementation, we also supplemented diets with sodium butyrate (NaB), Lalbaay(R), a NaB-containing supplement, acetate (AcOH), and valproate (VPA). FindingsMECP2 misexpression caused pre-eclosion lethality, thinning of larval skeletal fibers with nuclear mispositioning and altered mitochondria. Functionally, it reduced locomotion, decreased food transit and gut peristalsis. Phenotypes were strongest when expression began during development. NaB and VPA supplementation rescue most of these phenotypes, consistent with their histone-deacetylase (HDAC) activity. Defects were not observed upon comparable misexpression of an RTT-associated MeCP2 loss-of-function variant, indicating that they might be relevant to pathogenesis of MECP2-related disorders. InterpretationOur genetic in vivo analysis models peripheral effects of MeCP2 dysregulation and their amelioration, supporting the possibility of HDAC-targeted strategies for MECP2-related muscle and gastrointestinal dysfunction.

genetics↗

bioRxiv2025

TUSC3 serves as a rate-limiting gatekeeper of a glycan-mediated ER Triage Checkpoint for BMP4/Dpp

Trimming of the three glucose residues decorating nascent N-glycoproteins is a critical step for their entry into the endoplasmic reticulum quality control (ERQC) cycle and recognition by ER chaperones. However, the functional relevance of the second glucose (G2) and the regulatory step upstream of its removal by ER glucosidase II (GCS2) remains poorly understood. Here, we report that TUSC3, a component of the oligosaccharyltransferase (OST) complex, regulates G2 to G1 trimming on N-glycosylated bone morphogenetic protein 4 (BMP4) and its Drosophila homolog Dpp to promote their ERQC entry. Loss- and gain-of-function genetic experiments and biochemical assays in mammalian cells and flies indicate that TUSC3 serves as a dosage-sensitive gatekeeper that influences the decision between proper folding and secretion versus elimination by ER-associated degradation for BMP4 molecules, thereby tuning BMP signaling. Together, these data reveal an unrecognized role for an OST component in early glycoprotein maturation, relevant to a major developmental signaling pathway.

developmental biology↗

bioRxiv2025

Mechanical Cues Regulate Cargo Sorting and Export at the Golgi

The secretory pathway is a sophisticated endomembrane machinery designed to transport and deliver proteins and lipids to intracellular organelles and the extracellular space. While the molecular components of the secretory pathway are well understood, less is known about their regulation, especially by mechanical cues. Here, we report that substrate stiffness stimulates conventional secretion. We have unravelled a molecular pathway that links a mechanical cue through Src and FAK kinases to promote the trafficking of secretory proteins out of the Golgi apparatus and prevent their post-Golgi lysosomal degradation. Phosphoproteomic analysis revealed the Golgi-specific Brefeldin A resistance factor 1 (GBF1) as a key downstream mechano-responsive regulator, whose phosphorylation state orchestrates post-Golgi cargo sorting, directing proteins either toward secretion or to lysosomes. Finally, we identified AMPK as a stiffness-dependent upstream regulator of GBF1 phosphorylation. Together, our data reveal a molecular regulatory loop in which matrix stiffness positively regulates cellular secretion via the Src-FAK-AMPK-GBF1 axis, which can have relevant medical implications in conditions like cancer and fibrosis and their treatment.

cell biology↗

bioRxiv2023

Gut barrier defects, increased intestinal innate immune response, and enhanced lipid catabolism drive lethality in N-glycanase 1 deficient Drosophila

Intestinal barrier dysfunction leads to inflammation and associated metabolic changes. However, the relative impact of infectious versus non-infectious mechanisms on animal health in the context of barrier dysfunction is not well understood. Here, we establish that loss of Drosophila N-glycanase 1 (Pngl) leads to gut barrier defects, which cause starvation and increased JNK activity. These defects result in Foxo overactivation, which induces a hyperactive innate immune response and lipid catabolism, thereby contributing to lethality associated with loss of Pngl. Notably, germ-free rearing of Pngl mutants did not rescue lethality. In contrast, raising Pngl mutants on isocaloric, fat-rich diets improved animal survival in a dosage-dependent manner. Our data indicate that Pngl functions in Drosophila larvae to establish the gut barrier, and that the immune and metabolic consequences of loss of Pngl are primarily mediated through non-infectious mechanisms.

developmental biology↗