ArticleThe Journal of cell biology2022
NCOA4 drives ferritin phase separation to facilitate macroferritinophagy and microferritinophagy.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 119 citations in OpenAlex.
- The role of iron in normal and impaired testicular function.Andrology · 2026Review
- UCHL3 drives ferroptosis in nucleus pulposus cells by deubiquitinating HMGB1 to activate NCOA4-mediated ferritinophagy.Autophagy · 2026Article
- IDH-genotype-linked kinase rewiring accompanies enhanced therapeutic response to dual-drug ferritin nanocages in high-grade glioma.Materials today. Bio · 2026Article
- METTL14-Mediated N6-Methyladenosine Exacerbates Acute Lung Injury via USP30/NCOA4-Dependent Ferroptosis.MedComm · 2026Article
- Exosomal export of activated CASPASE-8 is linked to the prevention of TNF-induced cytotoxicity.Nature communications · 2026Article
- Endothelial progenitor cells-derived exosomes reduce ferroptosis and promote neovascularization after intracranial atherosclerosis in association with the NCOA4/FTH1 cascade modulation.Drug delivery and translational research · 2026Article
- An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death.Journal of cell science · 2026Article
- Timosaponin AIII-based liposomes loaded with Auranofin for the induction of ferroptosis in anaplastic thyroid carcinoma.Journal of cancer research and clinical oncology · 2026Article
- ADGRG1-targeted hypoxia preconditioned extracellular vesicles ameliorate intervertebral disc degeneration by delivering taurine to disrupt the oxidative stress feedback loop-driven ferroptosis in nucleus pulposus cells.Bioactive materials · 2026Article
- Pin1 targets phosphorylated NCOA4 for K29/K48-linked ubiquitination to suppress ferritinophagy and ferroptosis in anaplastic thyroid cancer.Cell death & disease · 2026Article
- Phosphorylation tunes p62 condensates to drive autophagic degradation of ubiquitinated proteins.The EMBO journal · 2026Article
- Liquid-liquid phase separation-driven regulated cell death: from molecular mechanisms to therapeutic strategies.Cell death discovery · 2026Review
- Cutting edge: ESCRT-mediated phagophore closure in mammals.The Biochemical journal · 2026Review
- Hepatokine ORM2 suppresses pathological ferritinophagy to prevent acute tissue injury.Cell death & disease · 2026Article
- The Interaction Between Iron and Selenium Affects Ferroptosis in Colorectal Cancer.International journal of molecular sciences · 2026Review
- NCOA4 initiates ferritinophagy by avidly binding GATE16 using two short linear interaction motifs.Life science alliance · 2026Article
- NCOA4-Mediated Ferritinophagy Induces Ferroptosis and Enriches Ferritin-Containing EVs via Ferritin Phase Separation to Promote Mechanical Ventilation-Induced Pulmonary Fibrosis.Journal of advanced research · 2026Article
- ELK1 suppressed the progression of vascular dementia via modulating mTOR/CREB/YAP/TFEB signaling induced ferroptosis in hippocampal cells.Scientific reports · 2026Article
- Elbasvir triggers ferroptosis in esophageal squamous cell carcinoma through NCOA4-mediated ferritinophagy.Medical oncology (Northwood, London, England) · 2026Article
- Electromagnetic fields regulate iron metabolism: From mechanisms to applications.Journal of advanced research · 2026Review
14 more citing papers are in PubMed but not listed here.
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5 authors at 2 institutions in 1 country.
Funding
Abstract
A ferritin particle consists of 24 ferritin proteins (FTH1 and FTL) and stores iron ions within it. During iron deficiency, ferritin particles are transported to lysosomes to release iron ions. Two transport pathways have been reported: macroautophagy and ESCRT-dependent endosomal microautophagy. Although the membrane dynamics of these pathways differ, both require NCOA4, which is thought to be an autophagy receptor for ferritin. However, it is unclear whether NCOA4 only acts as an autophagy receptor in ferritin degradation. Here, we found that ferritin particles form liquid-like condensates in a NCOA4-dependent manner. Homodimerization of NCOA4 and interaction between FTH1 and NCOA4 (i.e., multivalent interactions between ferritin particles and NCOA4) were required for the formation of ferritin condensates. Disruption of these interactions impaired ferritin degradation. Time-lapse imaging and three-dimensional correlative light and electron microscopy revealed that these ferritin-NCOA4 condensates were directly engulfed by autophagosomes and endosomes. In contrast, TAX1BP1 was not required for the formation of ferritin-NCOA4 condensates but was required for their incorporation into autophagosomes and endosomes. These results suggest that NCOA4 acts not only as a canonical autophagy receptor but also as a driver to form ferritin condensates to facilitate the degradation of these condensates by macroautophagy (i.e., macroferritinophagy) and endosomal microautophagy (i.e., microferritinophagy).
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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.