ArticleMolecular cell2020
Maintaining Iron Homeostasis Is the Key Role of Lysosomal Acidity for Cell Proliferation.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
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Who cites it
151 citing papers in PubMed, 241 citations in OpenAlex.
- Post-translational modification-regulating biomaterials for regeneration.Bioactive materials · 2026Review
- Lysosomal metabolism in pancreatic cancer and its crosstalk with host physiology.Genes & development · 2026Review
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Chemogenomic maps reveal a PRDX1-dependent iron-damage axis in the DNA damage response.Nature chemical biology · 2026Article
- Ion transport as a determinant of membrane fusion and fission.Nature structural & molecular biology · 2026Review
- Nano-formulations in therapeutic strategies targeting cancer ferroptosis.Journal of pharmaceutical analysis · 2026Review
- TLDc proteins: Stress-responsive nexus regulators of redox signaling, V-ATPase dynamics, and organellar crosstalk in neurodegeneration.Redox biology · 2026Review
- Subcellular regulation of ferroptosis: roles of individual intracellular organelles and cross talk.American journal of physiology. Cell physiology · 2026Review
- Established and emerging roles of lysosomal dysfunction in cardiac aging.Nature cardiovascular research · 2026Review
- Review
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- Organelle regulation of ferroptosis after intracerebral hemorrhage.Redox biology · 2026Review
- A Novel Nitric Oxide Donor Induced Ferroptosis in Drug-Resistant Ovarian Cancer Cells through Lysosomal Iron Metabolism Regulation and Lipid Peroxidation.ACS pharmacology & translational science · 2026Article
- Vacuole pH loss triggers ESCRT-dependent plasma membrane remodeling to prevent amino acid toxicity.bioRxiv : the preprint server for biology · 2026Article
- Article
- Organellar insights in ageing and longevity.Nature cell biology · 2026Review
- Mitochondrial iron overload is associated with lysosomal dysfunction-mediated mitophagy impairment in the heart of Friedreich's ataxia.Mitochondrion · 2026Article
- Redox cycling nitroxide limits cellular iron availability and selectively inhibits iron-sulfur cluster metabolism.Cell death discovery · 2026Article
- Hepatic STEAP4 promotes liver regeneration by regulating lysosomal iron homeostasis and membrane integrity in acetaminophen-induced liver injury.Hepatology (Baltimore, Md.) · 2026Article
- Elemental Composition and Degradation Rate Impact the Biocompatibility of Copper Chalcogenide Nanocrystals.ACS applied materials & interfaces · 2026Article
91 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The lysosome is an acidic multi-functional organelle with roles in macromolecular digestion, nutrient sensing, and signaling. However, why cells require acidic lysosomes to proliferate and which nutrients become limiting under lysosomal dysfunction are unclear. To address this, we performed CRISPR-Cas9-based genetic screens and identified cholesterol biosynthesis and iron uptake as essential metabolic pathways when lysosomal pH is altered. While cholesterol synthesis is only necessary, iron is both necessary and sufficient for cell proliferation under lysosomal dysfunction. Remarkably, iron supplementation restores cell proliferation under both pharmacologic and genetic-mediated lysosomal dysfunction. The rescue was independent of metabolic or signaling changes classically associated with increased lysosomal pH, uncoupling lysosomal function from cell proliferation. Finally, our experiments revealed that lysosomal dysfunction dramatically alters mitochondrial metabolism and hypoxia inducible factor (HIF) signaling due to iron depletion. Altogether, these findings identify iron homeostasis as the key function of lysosomal acidity for cell proliferation.
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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.