Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(11), P. 926 - 946

Published: Aug. 6, 2024

Language: Английский

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MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(3)

Published: Jan. 3, 2025

Many cancer cells exhibit increased amounts of paucimannose glycans, which are truncated N-glycan structures rarely found in mammals. Paucimannosidic proteins proposedly generated within lysosomes and exposed on the cell surface through a yet uncertain mechanism. In this study, we revealed that paucimannosidic produced by lysosomal glycosidases secreted via exocytosis. Interestingly, exocytosis preferentially occurred vicinity focal adhesions, protein complexes connecting actin cytoskeleton to extracellular matrix. Through genome-wide knockout screening, identified MYO18B, an crosslinker, is required for adhesion maturation, facilitating release milieu. Moreover, mechanosensitive cation channel PIEZO1 locally activated at adhesions imports Ca2+ necessary lysosome-plasma membrane fusion. Collectively, our study unveiled intimate relationship between adhesion, shedding light unexpected interplay activities cellular mechanosensing.

Language: Английский

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Cellular and organismal function of choline metabolism

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

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Experimental tools and emerging principles of organellar mechanotransduction

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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LYCHOS is a human hybrid of a plant-like PIN transporter and a GPCR

Nature, Journal Year: 2024, Volume and Issue: 634(8036), P. 1238 - 1244

Published: Oct. 2, 2024

Lysosomes have crucial roles in regulating eukaryotic metabolism and cell growth by acting as signalling platforms to sense respond changes nutrient energy availability

Language: Английский

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Cellular homeostatic responses to lysosomal damage

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Improved Black Phosphorus Nanocomposite Hydrogel for Bone Defect Repairing: Mechanisms for Advancing Osteogenesis

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Bone defects caused by fractures and diseases often do not heal spontaneously. They require external agents for repair regeneration. tissue engineering is emerging as a promising alternative to traditional therapies like autografts allografts. Nanobiomaterials enhance osteoblast resistance harsh environments promoting cell differentiation. Black phosphorus (BP), novel 2D material in biomedicine, displays unique osteogenic antimicrobial properties. However, BP nanosheets still face clinical limitations rapid degradation high-dose cytotoxicity. To address these, the introduction of amino-silicon phthalocyanine (SiPc-NH2) investigated see if it can dispersion, reduce oxidation, improve stability safety better osteogenesis antibacterial effects through noncovalent interactions (van der Waals, π-π stacking electrostatic interactions). Here, self-healing hydrogel successfully designed using step-by-step co-assembly SiPc-NH2. SiPc-NH2 "structural stabilizer" reconstructed well-dispersed BP-SiPc-NH2 nanosheets, which improves biocompatibility BP, reduces oxidation enhances photothermal conversion, guaranteeing Furthermore, findings show BP-SiPc-NH2-induced mitochondrial changes support regulating crosstalk between Hippo Wnt signaling pathways-mediated homeostasis, boosting cellular bioenergetics. Overall, this morphology-based strategy holds great promise bone applications.

Language: Английский

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Lysosomal Quality Control

Autophagy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Healthy cells need functional lysosomes to degrade cargo delivered by autophagy and endocytosis. Defective can lead severe conditions such as lysosomal storage diseases (LSDs) neurodegeneration. To maintain lysosome integrity functionality, have evolved multiple quality control pathways corresponding different types of stress damage. These be divided into five levels: regulation, reformation, repair, removal, replacement. The levels often work together the network. This review summarizes discusses less-studied area membrane protein regulation degradation, highlighting key unanswered questions in field.

Language: Английский

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Abnormal epigenetic modification of lysosome and lipid regulating genes in Alzheimer’s disease

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Background Abnormal lipid metabolism has been identified as a potential pathogenic mechanism of Alzheimer's disease (AD), which might be epigenetically regulated. Lysosomes are critical organelles for metabolism. However, the epigenetic modifications lysosome and regulating genes remain unclear in AD patients. Objective Explore role abnormal modifications, especially methylation metabolism-related AD. Methods Methylation beadchip MALDI-TOF mass spectrometry were used to detect genome-wide DNA levels validate key gene methylation, respectively. Clinical data collected from all participants. Associations between clinical biochemical characteristics altered patients analyzed, risk factor model was established. Results 41 differentially methylated positions (DMPs) corresponding 33 patients, with 18 hypermethylated 23 hypomethylated positions. Significant alterations observed ( CTNNB1, DGKQ, SLC27A1 ) lysosomal transmembrane TMEM175 ). analysis revealed that TP, ALB, IB, ADA, ALP, HCY, GLU, TC, BUN, HDL-C, LDL-C, APOA1 significantly higher whereas A/G DB lower. hypermethylation further verified found correlate APOA1, HCY. The AUC model, integrated markers reached 0.9519 p < 0.0001). Conclusions regulation dyshomeostasis high-risk factors processes pathogenesis.

Language: Английский

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Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity

Cell Reports, Journal Year: 2024, Volume and Issue: 43(6), P. 114326 - 114326

Published: June 1, 2024

Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting fetal brain programming could permit screening and intervention. We used lineage tracing to demonstrate the shared ontogeny between macrophages (microglia) placental (Hofbauer cells) a mouse model maternal diet-induced obesity, single-cell RNA-seq transcriptional programs. Comparison human datasets demonstrated conservation resident macrophage signatures mice humans. Single-cell identified common alterations Hofbauer cell gene expression induced as well sex differences these alterations. propose that cells, which are easily accessible at birth, provide insights into programs may facilitate early vulnerable disorders.

Language: Английский

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