ArticleNature metabolism2023
A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
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- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- PSAP Protects Against Acute Myocardial Ischemia-Reperfusion Injury by Promoting ASAH1-Mediated Ceramide Metabolism.Journal of cardiovascular translational research · 2026Article
- Two lysosomal genes ATP13A2 and GBA1 interact to drive neurodegeneration.Molecular neurodegeneration · 2026Article
- The mitochondrial trans-2-enoyl-CoA reductase is necessary for mitochondrial homeostasis in C. elegans.Genetics · 2025Article
- A mouse model of MEPAN demonstrates a role for mitochondrial fatty acid synthesis in iron-sulfur cluster and supercomplex formation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Developing a thyroid cancer differentiation state classification system using deep residual networks and metabolic signature profiling.NPJ digital medicine · 2025Article
- Glia-derived noncanonical fatty acid binding protein modulates brain lipid storage and clearance.Science advances · 2025Article
- Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Disruption of sulfur transferase complex increases bacterial intramacrophage persistence.PLoS pathogens · 2025Article
- Identification of DownregulatedInternational journal of molecular sciences · 2025Article
- Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.Nature neuroscience · 2024Article
- Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes.International journal of molecular sciences · 2024Review
- Loss of the endoplasmic reticulum protein Tmem208 affects cell polarity, development, and viability.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.Cell metabolism · 2024Review
- Application of deep brain stimulation for the treatment of childhood-onset dystonia in patients with MEPAN syndrome.Frontiers in neurology · 2023Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
In most eukaryotic cells, fatty acid synthesis (FAS) occurs in the cytoplasm and in mitochondria. However, the relative contribution of mitochondrial FAS (mtFAS) to the cellular lipidome is not well defined. Here we show that loss of function of Drosophila mitochondrial enoyl coenzyme A reductase (Mecr), which is the enzyme required for the last step of mtFAS, causes lethality, while neuronal loss of Mecr leads to progressive neurodegeneration. We observe a defect in Fe-S cluster biogenesis and increased iron levels in flies lacking mecr, leading to elevated ceramide levels. Reducing the levels of either iron or ceramide suppresses the neurodegenerative phenotypes, indicating an interplay between ceramide and iron metabolism. Mutations in human MECR cause pediatric-onset neurodegeneration, and we show that human-derived fibroblasts display similar elevated ceramide levels and impaired iron homeostasis. In summary, this study identifies a role of mecr/MECR in ceramide and iron metabolism, providing a mechanistic link between mtFAS and neurodegeneration.
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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.