ArticleThe Journal of biological chemistry2018
Acute loss of iron-sulfur clusters results in metabolic reprogramming and generation of lipid droplets in mammalian cells.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 103 citations in OpenAlex.
- Ferritinophagy Rewires Carnitine-Dependent Lipid Metabolism to Inhibit PRRSV and IAV Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Long-read methylome analysis of Oleidesulfovibrio alaskensis G20 biofilm under copper stress.Scientific reports · 2025Article
- Metabolic and imaging phenotypes associated withbioRxiv : the preprint server for biology · 2025Article
- Targeting metabolic vulnerability by combining NAMPT inhibitors and disulfiram for treatment of recurrent ovarian cancer.Cell death & disease · 2025Article
- Why cells need iron: a compendium of iron utilisation.Trends in endocrinology and metabolism: TEM · 2024Review
- Functional analysis of the whole CYPome and Fdxome ofEngineering microbiology · 2024Article
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- Engineering acyclovir-induced RNA nanodevices for reversible and tunable control of aptamer function.Cell chemical biology · 2024Article
- Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation.Biomedicines · 2024Review
- Multi-layered metabolic effects of trehalose on the liver proteome in apoE-knockout mice model of liver steatosis.Pharmacological reports : PR · 2024Article
- CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC.Nature communications · 2024Article
- METTL17 is an Fe-S cluster checkpoint for mitochondrial translation.Molecular cell · 2024Article
- Iron promotes glycolysis to drive colon tumorigenesis.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
- A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels.Nature metabolism · 2023Article
- The Fe-S cluster assembly protein IscU2 increases α-ketoglutarate catabolism and DNA 5mC to promote tumor growth.Cell discovery · 2023Article
- Adenylosuccinic Acid: An Orphan Drug with Untapped Potential.Pharmaceuticals (Basel, Switzerland) · 2023Article
- The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective.Biomolecules · 2023Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Iron-sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant-negative variants of the primary Fe-S biogenesis scaffold protein iron-sulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming associated with loss of Fe-S-containing proteins in several major cellular compartments. Using multiple metabolomics platforms, we observed a ∼12-fold increase in intracellular citrate content in Fe-S-deficient cells, a surge that was due to loss of aconitase activity. The excess citrate was generated from glucose-derived acetyl-CoA, and global analysis of cellular lipids revealed that fatty acid biosynthesis increased markedly relative to cellular proliferation rates in Fe-S-deficient cells. We also observed intracellular lipid droplet accumulation in both acutely Fe-S-deficient cells and iron-starved cells. We conclude that deficient Fe-S biogenesis and acute iron deficiency rapidly increase cellular citrate concentrations, leading to fatty acid synthesis and cytosolic lipid droplet formation. Our findings uncover a potential cause of cellular steatosis in nonadipose tissues.
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