ArticleThe EMBO journal2017
VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy.
Article in The EMBO journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 233 papers, 2 of them syntheses that pooled it.
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Who cites it
233 citing papers in PubMed, 2 syntheses or guidelines pooled it, 350 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Selective autophagy of intracellular organelles: recent research advances.Theranostics · 2021Pooled it
- DFCP1-containing ER microdomains mediate lysosomal membrane repair.Nature cell biology · 2026Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- The role of E3 ubiquitin ligases in selective types of macroautophagy.EMBO reports · 2026Review
- FAF1 and FAF2 enhance unfolding by p97-UFD1-NPL4 complex enabling rational design of p97 activators.The EMBO journal · 2026Article
- Disruption of iron metabolism resulting from Dmt1/Slc11a2 deficiency compromises Notch protein degradation and transcriptional activation.The FEBS journal · 2026Article
- Review
- Global cellular responses to lysosomal damage.Current biology : CB · 2026Review
- Article
- The p97 adaptor p47/NSFL1C is necessary for stress granule dissolution after heat stress.bioRxiv : the preprint server for biology · 2026Article
- ASPL-driven subunit exchange remodels VCP/p97 hexamers and is impaired by a multisystem proteinopathy mutation.bioRxiv : the preprint server for biology · 2026Article
- Direct observation of ATP-driven ubiquitin chain handling by Cdc48.Nature communications · 2026Article
- Development and Structural Characterization of UTE-156, a Covalent Inhibitor of the VCP/p97 AAA+ ATPase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Energy-sensing molecule RORγ regulates cholesterol metabolism and immune signaling in diabetic kidney disease and aging.Nature communications · 2026Article
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Differential regulation of p62-ubiquitin conjugates in neurons versus astrocytes during cellular stress.PloS one · 2026Article
- Proteomic and Ubiquitinated Proteome Insights Into ER Stress Responses in Chinese Hamster Ovary Cells Under Mild Hypothermic Conditions.Biotechnology and bioengineering · 2026Article
- From homeostasis to pathology, organelle-specific autophagy in skeletal muscle: a PRISMA-ScR scoping review.Frontiers in physiology · 2026Review
173 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin-directed AAA-ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. Together, they act downstream of K63-linked ubiquitination and p62 recruitment, and selectively remove K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation. Lysosomal clearance is also compromised in MEFs harboring a p97 mutation that causes inclusion body myopathy and neurodegeneration, and damaged lysosomes accumulate in affected patient tissue carrying the mutation. Moreover, we show that p97 helps clear late endosomes/lysosomes ruptured by endocytosed tau fibrils. Thus, our data reveal an important mechanism of how p97 maintains lysosomal homeostasis, and implicate the pathway as a modulator of degenerative diseases.
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Registered trials
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.