ArticleThe Journal of biological chemistry2016
Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) Mutation and TRAP1 Inhibitor Gamitrinib-triphenylphosphonium (G-TPP) Induce a Forkhead Box O (FOXO)-dependent Cell Protective Signal from Mitochondria.
Article in The Journal of biological chemistry, 2016. 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, 43 citations in OpenAlex.
- TRAP1 and its therapeutic potential.Bioorganic & medicinal chemistry letters · 2025Review
- Quantitative proteomics analysis reveals the key proteins related to semen quality in Niangya yaks.Proteome science · 2023Article
- The development of cancers research based on mitochondrial heat shock protein 90.Frontiers in oncology · 2023Review
- Mitochondrial Control in Inflammatory Gastrointestinal Diseases.International journal of molecular sciences · 2022Review
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- TRAP1 Chaperones the Metabolic Switch in Cancer.Biomolecules · 2022Review
- TRAP1 in Oxidative Stress and Neurodegeneration.Antioxidants (Basel, Switzerland) · 2021Review
- Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model.International journal of molecular sciences · 2021Article
- Decoding the rosetta stone of mitonuclear communication.Pharmacological research · 2020Review
- Cytochrome C Oxidase Subunit 4 (COX4): A Potential Therapeutic Target for the Treatment of Medullary Thyroid Cancer.Cancers · 2020Article
- Mitochondrial retrograde signalling in neurological disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Article
- Role of Glucose Metabolism Reprogramming in the Pathogenesis of Cholangiocarcinoma.Frontiers in medicine · 2020Review
- Assessment of mitophagy in mt-KeimaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The Alpha Isoform of Heat Shock Protein 90 and the Co-chaperones p23 and Cdc37 Promote Opioid Anti-nociception in the Brain.Frontiers in molecular neuroscience · 2019Article
- Review
- Potential Therapeutic Drugs for Parkinson's Disease Based on Data Mining and Bioinformatics Analysis.Parkinson's disease · 2018Article
- Proteomic interrogation of HSP90 and insights for medical research.Expert review of proteomics · 2017Review
- Role of FOXO transcription factors in crosstalk between mitochondria and the nucleus.Journal of bioenergetics and biomembranes · 2017Review
- Isocitrate protects DJ-1 null dopaminergic cells from oxidative stress through NADP+-dependent isocitrate dehydrogenase (IDH).PLoS genetics · 2017Article
- Transgenic Expression of the Mitochondrial Chaperone TNFR-associated Protein 1 (TRAP1) Accelerates Prostate Cancer Development.The Journal of biological chemistry · 2016Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TRAP1 (tumor necrosis factor receptor-associated protein 1), a mitochondrial Hsp90 family chaperone, has been identified as a critical regulator of cell survival and bioenergetics in tumor cells. To discover novel signaling networks regulated by TRAP1, we generated Drosophila TRAP1 mutants. The mutants successfully developed into adults and produced fertile progeny, showing that TRAP1 is dispensable in development and reproduction. Surprisingly, mutation or knockdown of TRAP1 markedly enhanced Drosophila survival under oxidative stress. Moreover, TRAP1 mutation ameliorated mitochondrial dysfunction and dopaminergic (DA) neuron loss induced by deletion of a familial Parkinson disease gene PINK1 (Pten-induced kinase 1) in Drosophila. Gamitrinib-triphenylphosphonium, a mitochondria-targeted Hsp90 inhibitor that increases cell death in HeLa and MCF7 cells, consistently inhibited cell death induced by oxidative stress and mitochondrial dysfunction induced by PINK1 mutation in mouse embryonic fibroblast cells and DA cell models such as SH-SY5Y and SN4741 cells. Additionally, gamitrinib-triphenylphosphonium also suppressed the defective locomotive activity and DA neuron loss in Drosophila PINK1 null mutants. In further genetic analyses, we showed enhanced expression of Thor, a downstream target gene of transcription factor FOXO, in TRAP1 mutants. Furthermore, deletion of FOXO almost nullified the protective roles of TRAP1 mutation against oxidative stress and PINK1 mutation. These results strongly suggest that inhibition of the mitochondrial chaperone TRAP1 generates a retrograde cell protective signal from mitochondria to the nucleus in a FOXO-dependent manner.
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