ArticleThe EMBO journal2022
Cholesterol transfer via endoplasmic reticulum contacts mediates lysosome damage repair.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 154 citations in OpenAlex.
- GSK3β inhibits the differentiation of follicular granulosa cells by promoting lipid accumulation through autophagy in chickens.Poultry science · 2026Article
- DFCP1-containing ER microdomains mediate lysosomal membrane repair.Nature cell biology · 2026Article
- Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria.Nature communications · 2026Article
- Phosphatidylinositol 4-kinase as a target of pathogens-friend or foe?FEBS letters · 2026Review
- Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons.iScience · 2026Article
- Article
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- The ALS- and FTD-associated proteins annexin A11 and CHMP2B act sequentially in plasma membrane repair.Developmental cell · 2026Article
- VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair.Nature communications · 2026Article
- Endosomes as central hubs of interorganellar communication and cellular homeostasis.Protein & cell · 2026Review
- Cell surface liposome binding (CLiB) allows lipid-binding probe engineering via high-throughput screening.Nature cell biology · 2026Article
- Article
- Structural Mechanism and Cellular Restriction of Tau Seeding from Endolysosomes.bioRxiv : the preprint server for biology · 2026Article
- Ca²⁺ leakage is a conserved signal for non-canonical ATG8/LC3 lipidation and membrane repair.The EMBO journal · 2026Article
- Restoration of lysosomal membrane integrity in cell models of Pompe disease depends on fatty acid synthase and its product palmitic acid.Cellular & molecular biology letters · 2026Article
- Autophagosome turnover requires Arp2/3 complex-mediated maintenance of lysosomal integrity.Molecular biology of the cell · 2026Article
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- OSBPL10 alleviates neuronal ferroptosis via lysosomal membrane repair in a PS-dependent manner after spinal cord injury.Journal of neuroinflammation · 2026Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysosome integrity is essential for cell viability, and lesions in lysosome membranes are repaired by the ESCRT machinery. Here, we describe an additional mechanism for lysosome repair that is activated independently of ESCRT recruitment. Lipidomic analyses showed increases in lysosomal phosphatidylserine and cholesterol after damage. Electron microscopy demonstrated that lysosomal membrane damage is rapidly followed by the formation of contacts with the endoplasmic reticulum (ER), which depends on the ER proteins VAPA/B. The cholesterol-binding protein ORP1L was recruited to damaged lysosomes, accompanied by cholesterol accumulation by a mechanism that required VAP-ORP1L interactions. The PtdIns 4-kinase PI4K2A rapidly produced PtdIns4P on lysosomes upon damage, and knockout of PI4K2A inhibited damage-induced accumulation of ORP1L and cholesterol and led to the failure of lysosomal membrane repair. The cholesterol-PtdIns4P transporter OSBP was also recruited upon damage, and its depletion caused lysosomal accumulation of PtdIns4P and resulted in cell death. We conclude that ER contacts are activated on damaged lysosomes in parallel to ESCRTs to provide lipids for membrane repair, and that PtdIns4P generation and removal are central in this response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.