ArticleBMC biology2020
The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in mitochondrial metabolic homeostasis.
Article in BMC biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 90 citations in OpenAlex.
- Coordinated regulation of the metaboproteome by Hsp90 chaperones controls metabolic plasticity.iScience · 2026Article
- Review
- Rearrangement of the Cell Chaperone Machinery in Human Fibrosarcoma HT1080 Cells With the Knocked-Out HSP90AA1 Gene Encoding Hsp90α.Biology of the cell · 2026Article
- TRAP1 and its therapeutic potential.Bioorganic & medicinal chemistry letters · 2025Review
- Melatonin Supplementation Relieves Fluoride-Induced Bone Injury via Ion Homeostasis Disorder and PINK1/Parkin-Mediated Mitophagy.Foods (Basel, Switzerland) · 2025Article
- Cancer suppresses mitochondrial chaperone activity in macrophages to drive immune evasion.Nature immunology · 2025Article
- Mitochondrial HSP90 Paralog TRAP1 Deletion Drives Glutamine Addiction in Tumor Cells via Destablization of the Cys/Glu Antiporter SLC7A11/xCT.Molecular cancer research : MCR · 2025Article
- TRAP1 expression elicits pro-tumoral functions in macrophages associated to malignant peripheral nerve sheath tumor cells.Journal of experimental & clinical cancer research : CR · 2025Article
- Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating the Wnt/β-catenin signaling pathway in lung cancer.Histology and histopathology · 2025Article
- ATP plays a structural role in Hsp90 function.Nature communications · 2025Article
- Review
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- Pirh2 modulates the mitochondrial function and cytochrome c-mediated neuronal death during Alzheimer's disease.Cell death & disease · 2024Article
- Chaperones-A New Class of Potential Therapeutic Targets in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Structural and functional complexity of HSP90 in cellular homeostasis and disease.Nature reviews. Molecular cell biology · 2023Review
- Elucidation of novel TRAP1-Selective inhibitors that regulate mitochondrial processes.European journal of medicinal chemistry · 2023Article
- TRAP1 inhibits MARCH5-mediated MIC60 degradation to alleviate mitochondrial dysfunction and apoptosis of cardiomyocytes under diabetic conditions.Cell death and differentiation · 2023Article
- Inhibition of TRAP1 Accelerates the DNA Damage Response, Activation of the Heat Shock Response and Metabolic Reprogramming in Colon Cancer Cells.Frontiers in bioscience (Landmark edition) · 2023Article
- Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins.Genome research · 2023Article
- An evolving view of complex II-noncanonical complexes, megacomplexes, respiration, signaling, and beyond.The Journal of biological chemistry · 2023Review
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe molecular chaperone TRAP1, the mitochondrial isoform of cytosolic HSP90, remains poorly understood with respect to its pivotal role in the regulation of mitochondrial metabolism. Most studies have found it to be an inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) and an inducer of the Warburg phenotype of cancer cells. However, others have reported the opposite, and there is no consensus on the relevant TRAP1 interactors. This calls for a more comprehensive analysis of the TRAP1 interactome and of how TRAP1 and mitochondrial metabolism mutually affect each other.
resultsWe show that the disruption of the gene for TRAP1 in a panel of cell lines dysregulates OXPHOS by a metabolic rewiring that induces the anaplerotic utilization of glutamine metabolism to replenish TCA cycle intermediates. Restoration of wild-type levels of OXPHOS requires full-length TRAP1. Whereas the TRAP1 ATPase activity is dispensable for this function, it modulates the interactions of TRAP1 with various mitochondrial proteins. Quantitatively by far, the major interactors of TRAP1 are the mitochondrial chaperones mtHSP70 and HSP60. However, we find that the most stable stoichiometric TRAP1 complex is a TRAP1 tetramer, whose levels change in response to both a decline and an increase in OXPHOS.
conclusionsOur work provides a roadmap for further investigations of how TRAP1 and its interactors such as the ATP synthase regulate cellular energy metabolism. Our results highlight that TRAP1 function in metabolism and cancer cannot be understood without a focus on TRAP1 tetramers as potentially the most relevant functional entity.
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