ArticleProceedings of the National Academy of Sciences of the United States of America2015
The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic targets in breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 80 citations in OpenAlex.
- RanBP2 promotes ferroptosis resistance and compromises therapeutic response by stabilizing SLC7A1 through LRSAM1 SUMOylation and ubiquitination in lung adenocarcinoma.Cell death and differentiation · 2026Article
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Medicinal Chemistry Review of the NEET Protein Family.ChemMedChem · 2026Review
- Exploring CISD1 as a multifaceted biomarker in cancer: Implications for diagnosis, prognosis, and immunotherapeutic response.Genes & diseases · 2025Article
- Article
- CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Micronutrient Status and Breast Cancer: A Narrative Review.International journal of molecular sciences · 2024Review
- Mitochondria-related signaling pathways involved in breast cancer regulate ferroptosis.Genes & diseases · 2024Review
- Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker.Frontiers in oncology · 2024Review
- Targeting the initiator to activate both ferroptosis and cuproptosis for breast cancer treatment: progress and possibility for clinical application.Frontiers in pharmacology · 2024Review
- Electron transfer activity of the nanodisc-bound mitochondrial outer membrane protein mitoNEET.Free radical biology & medicine · 2022Article
- An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters.Communications biology · 2022Article
- A VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Nitric oxide reversibly binds the reduced [2Fe-2S] cluster in mitochondrial outer membrane protein mitoNEET and inhibits its electron transfer activity.Frontiers in molecular biosciences · 2022Article
- Multiple Poses and Thermodynamics of Ligands Targeting Protein Surfaces: The Case of Furosemide Binding to mitoNEET in Aqueous Solution.Frontiers in cell and developmental biology · 2022Article
- Gambogic acid: Multi-gram scale isolation, stereochemical erosion toward epi-gambogic acid and biological profile.Frontiers in natural products · 2022Article
- Overexpression of CISD1 Predicts Worse Survival in Hepatocarcinoma Patients.BioMed research international · 2022Article
- Loss of the redox mitochondrial protein mitoNEET leads to mitochondrial dysfunction in B-cell acute lymphoblastic leukemia.Free radical biology & medicine · 2021Article
- Mitochondrial iron-sulfur clusters: Structure, function, and an emerging role in vascular biology.Redox biology · 2021Review
- Iron-Sulfur Cluster Biogenesis as a Critical Target in Cancer.Antioxidants (Basel, Switzerland) · 2021Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Identification of novel drug targets and chemotherapeutic agents is a high priority in the fight against cancer. Here, we report that MAD-28, a designed cluvenone (CLV) derivative, binds to and destabilizes two members of a unique class of mitochondrial and endoplasmic reticulum (ER) 2Fe-2S proteins, mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1), recently implicated in cancer cell proliferation. Docking analysis of MAD-28 to mNT/NAF-1 revealed that in contrast to CLV, which formed a hydrogen bond network that stabilized the 2Fe-2S clusters of these proteins, MAD-28 broke the coordinative bond between the His ligand and the cluster's Fe of mNT/NAF-1. Analysis of MAD-28 performed with control (Michigan Cancer Foundation; MCF-10A) and malignant (M.D. Anderson-metastatic breast; MDA-MB-231 or MCF-7) human epithelial breast cells revealed that MAD-28 had a high specificity in the selective killing of cancer cells, without any apparent effects on normal breast cells. MAD-28 was found to target the mitochondria of cancer cells and displayed a surprising similarity in its effects to the effects of mNT/NAF-1 shRNA suppression in cancer cells, causing a decrease in respiration and mitochondrial membrane potential, as well as an increase in mitochondrial iron content and glycolysis. As expected, if the NEET proteins are targets of MAD-28, cancer cells with suppressed levels of NAF-1 or mNT were less susceptible to the drug. Taken together, our results suggest that NEET proteins are a novel class of drug targets in the chemotherapeutic treatment of breast cancer, and that MAD-28 can now be used as a template for rational drug design for NEET Fe-S cluster-destabilizing anticancer drugs.
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Registered trials
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.