ArticleNature metabolism2025
BDH2-driven lysosome-to-mitochondria iron transfer shapes ferroptosis vulnerability of the melanoma cell states.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Ferroptosis: significance to zoonotic diseases and therapeutic prospects.Emerging microbes & infections · 2026Review
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 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
- Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.Biomolecules · 2026Review
- Toxic Metal-Essential Trace Element Imbalance in Cardiometabolic Disease: Ferroptosis as a Mechanistic Link Between Environmental Exposure and Vascular Injury.Cardiovascular toxicology · 2026Review
- An iron logic unites bacterial and cancer persister cells.Nature reviews. Molecular cell biology · 2026Article
- Crystallinity-Gradient Etched Hollow Mesoporous Zinc Nanoparticle for Dual-Source HAdvanced healthcare materials · 2026Article
- Elevated ferroptosis is associated with elevated T cells in patients with heat stroke.Molecular biology reports · 2026Article
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- Heme Oxygenase-1 Differentially Controls Pigmentation in Physiological and Pathological Melanogenesis.Pigment cell & melanoma research · 2026Article
- CoQExperimental & molecular medicine · 2026Review
- Stress granules shape ferroptosis in cancer.Nature cell biology · 2026Article
- BZW1 Drives Immune Evasion in Lung Adenocarcinoma via Ferroptosis Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Organelle contact sites in cancer cells.Cell death & disease · 2026Review
- In Situ Synthesis of Covalent Organic Frameworks Inside Cells for Triggering Ferroptosis and Immunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Multi-layered integrated shielding: engineering ferroptosis-resistant mesenchymal stem cells for precision therapy of intervertebral disc degeneration.Apoptosis : an international journal on programmed cell death · 2026Review
- FSP1 and histone deacetylases suppress cancer persister cell ferroptosis.Science advances · 2026Article
- NCOA4 as a regulatory switch linking DNA damage to lipid peroxidation in radiation response.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
Iron sustains cancer cell plasticity, yet it also sensitizes the mesenchymal, drug-tolerant phenotype to ferroptosis. This posits that iron compartmentalization must be tightly regulated. However, the molecular machinery governing organelle Fe(II) compartmentalization remains elusive. Here, we show that BDH2 is a key effector of inter-organelle Fe(II) redistribution and ferroptosis vulnerability during melanoma transition from a melanocytic (MEL) to a mesenchymal-like (MES) phenotype. In MEL cells, BDH2 localizes at the mitochondria-lysosome contacts (MLCs) to generate the siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA), which ferries iron into the mitochondria. Fe(II) transfer by BDH2 supports mitochondrial bioenergetics, which is required to maintain lysosomal acidification and MLC formation. Loss of BDH2 alters lysosomal pH and MLC tethering dynamics, causing lysosomal iron sequestration, which primes MES cells for ferroptosis. Rescuing BDH2 expression, or supplementing 2,5-DHBA, rectifies lysosomal pH and MLCs, protecting MES cells from ferroptosis and enhancing their ability to metastasize. Thus, we unveil a BDH2-dependent mechanism that orchestrates inter-organelle Fe(II) transfer, linking metabolic regulation of lysosomal pH to the ferroptosis vulnerability of the mesenchymal, drug-tolerant cancer cells.
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