ArticleThe Journal of biological chemistry2014
4-methylene-2-octyl-5-oxotetrahydrofuran-3-carboxylic acid (C75), an inhibitor of fatty-acid synthase, suppresses the mitochondrial fatty acid synthesis pathway and impairs mitochondrial function.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- Gravitational and mechanical forces shape mitochondrial translation.Nature communications · 2026Article
- METTL16-mBMC biology · 2026Article
- FASN regulates CSE-induced apoptosis, oxidative stress and mitochondrial damage in type 2 alveolar epithelial cells by regulating NRF2 expression and nuclear translocation.Redox report : communications in free radical research · 2025Article
- Targeting cancer metabolism: Therapeutic potential of the fatty acid synthase (FASN) inhibitors.Critical reviews in oncology/hematology · 2025Review
- The somatic genome of Eptatretus okinoseanus reveals the adaptation to deep-sea oligotrophic environment.BMC genomics · 2024Article
- Fatty acid synthase inhibition improves hypertension-induced erectile dysfunction by suppressing oxidative stress and NLRP3 inflammasome-dependent pyroptosis through activating the Nrf2/HO-1 pathway.Frontiers in immunology · 2024Article
- Lipid metabolism in dendritic cell biology.Immunological reviews · 2023Review
- Alternative splicing liberates a cryptic cytoplasmic isoform of mitochondrial MECR that antagonizes influenza virus.PLoS biology · 2022Article
- Proteomic Signatures of Microbial Adaptation to the Highest Ultraviolet-Irradiation on Earth: Lessons From a Soil Actinobacterium.Frontiers in microbiology · 2022Article
- Sulforaphane downregulated fatty acid synthase and inhibited microtubule-mediated mitophagy leading to apoptosis.Cell death & disease · 2021Article
- Genetic dissection of the mitochondrial lipoylation pathway in yeast.BMC biology · 2021Article
- Article
- Fatty Acid Synthase Contributes to Restimulation-Induced Cell Death of Human CD4 T Cells.Frontiers in molecular biosciences · 2019Article
- Metabolic Control of Dendritic Cell Functions: Digesting Information.Frontiers in immunology · 2019Review
- An unexpected link between fatty acid synthase and cholesterol synthesis in proinflammatory macrophage activation.The Journal of biological chemistry · 2018Article
- Article
- MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder.American journal of human genetics · 2016Article
- [6]-Gingerol inhibits de novo fatty acid synthesis and carnitine palmitoyltransferase-1 activity which triggers apoptosis in HepG2.American journal of cancer research · 2015Article
- Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7.Evidence-based complementary and alternative medicine : eCAM · 2015Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
4-Methylene-2-octyl-5-oxotetrahydrofuran-3-carboxylic acid (C75) is a synthetic fatty-acid synthase (FASN) inhibitor with potential therapeutic effects in several cancer models. Human mitochondrial β-ketoacyl-acyl carrier protein synthase (HsmtKAS) is a key enzyme in the newly discovered mitochondrial fatty acid synthesis pathway that can produce the substrate for lipoic acid (LA) synthesis. HsmtKAS shares conserved catalytic domains with FASN, which are responsible for binding to C75. In our study, we explored the possible effect of C75 on HsmtKAS and mitochondrial function. C75 treatment decreased LA content, impaired mitochondrial function, increased reactive oxygen species content, and reduced cell viability. HsmtKAS but not FASN knockdown had an effect that was similar to C75 treatment. In addition, an LA supplement efficiently inhibited C75-induced mitochondrial dysfunction and oxidative stress. Overexpression of HsmtKAS showed cellular protection against low dose C75 addition, whereas there was no protective effect upon high dose C75 addition. In summary, the mitochondrial fatty acid synthesis pathway has a vital role in mitochondrial function. Besides FASN, C75 might also inhibit HsmtKAS, thereby reducing LA production, impairing mitochondrial function, and potentially having toxic effects. LA supplements sufficiently ameliorated the toxicity of C75, showing that a combination of C75 and LA may be a reliable cancer treatment.
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