ArticleScience (New York, N.Y.)2025
LYVAC/PDZD8 is a lysosomal vacuolator.
Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- DFCP1-containing ER microdomains mediate lysosomal membrane repair.Nature cell biology · 2026Article
- Ion transport as a determinant of membrane fusion and fission.Nature structural & molecular biology · 2026Review
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair.Nature communications · 2026Article
- Cell surface liposome binding (CLiB) allows lipid-binding probe engineering via high-throughput screening.Nature cell biology · 2026Article
- Live cell imaging reveals paclitaxel-induced lysosome motility and function disruption in DRG neurons.bioRxiv : the preprint server for biology · 2026Article
- How endosomal PIKfyve inhibition prevents viral membrane fusion and entry.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Microglial cholesterol reprogramming drives cognitive impairment under hypobaric hypoxia.Journal of neuroinflammation · 2026Article
- Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- Membrane atg8ylation and autophagy in protection against Mycobacterium tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Pathogen-Induced Lysosomal Membrane Permeabilization: A Critical Interface Between Host Defense and Cell Death.International journal of molecular sciences · 2026Review
- Review
- Disruption of the PIKfyve complex unveils an adaptive mechanism to promote lysosomal repair and mitochondrial homeostasis.Nature communications · 2025Article
- How endosomal PIKfyve inhibition prevents viral membrane fusion and entry.bioRxiv : the preprint server for biology · 2025Article
- LRRK2 integrates Rab and GABARAP interactions to sense and respond to distinct lysosomal stresses.bioRxiv : the preprint server for biology · 2025Article
- Mechanism of phosphoinositide regulation of lysosomal pH via inhibition of CLC-7.bioRxiv : the preprint server for biology · 2025Article
- LYVAC/PDZD8 is a lysosomal vacuolator.Science (New York, N.Y.) · 2025Article
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8 authors.
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Abstract
Lysosomal vacuolation is commonly found in many pathophysiological conditions, but its molecular mechanisms and functions remain largely unknown. Here, we show that the endoplasmic reticulum (ER)-anchored lipid transfer protein PDZ domain-containing 8 (PDZD8), which we propose to be renamed as lysosomal vacuolator (LYVAC), is a general mediator of lysosomal vacuolation. Using human cell lines, we found that diverse lysosomal vacuolation inducers converged on lysosomal osmotic stress, triggering LYVAC recruitment through multivalent interactions. Stress-induced lysosomal lipid signaling contributed to both the recruitment and activation of LYVAC. By directly sensing lysosomal phosphatidylserine and cholesterol, the lipid transfer domain of LYVAC mediated directional ER-to-lysosome lipid movement, leading to osmotic membrane expansion of lysosomes. These findings uncover an essential mechanism for lysosomal vacuolation with broad implications in pathophysiology.
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