ArticleThe Journal of clinical investigation2022
A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 77 citations in OpenAlex.
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- The mitochondrial chaperone HSPD1 folds MTHFD2 independently of its co-chaperone HSPE1.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Article
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- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Crosstalk collapse: mitochondria-centric organelle network disruption in ovarian aging.Cell communication and signaling : CCS · 2026Review
- Synphilin-1 Is Essential for Cytoskeletal Integrity of Brain Ventricular Cilia and Mitochondrial Proteostasis.International journal of molecular sciences · 2026Article
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- Radiation-induced autophagy regulates fibroblast mitochondrial metabolism and crosstalk with triple-negative breast cancer cells.Cell reports · 2026Article
- Dusp15 modulates mtHsp70 Thr116 phosphorylation state to preserve mito-UPR and attenuate cardiac dysfunction in diabetic cardiomyopathy.Cardiovascular diabetology · 2026Article
- Fibrinogen exacerbates α-synuclein aggregation and mitochondrial dysfunction via alpha5beta3 integrin in Parkinson's disease.Journal of advanced research · 2026Article
- A panel of four autoantibodies to tumour-associated antigens in patients with prostate cancer and its potential for multi-cancer detection.British journal of cancer · 2026Article
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
- CDC25C downregulation suppresses HCC growth via mitochondrial stress-induced autophagy and apoptosis.Scientific reports · 2026Article
- NMR based human gut metabolomic profiling reveals altered metabolites associated with pulmonary and extra-pulmonary tuberculosis.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer.British journal of cancer · 2025Article
- Integrative analysis of molecular mechanisms in prostate cancer via single-cell RNA sequencing and weighted gene co-expression network analysis.Scientific reports · 2025Article
- Identification of genes related to the effects of bicalutamide and zoladex on benign prostatic hyperplasia.Scientific reports · 2025Article
- Mitochondrial Protease ClpP: Cancer Marker and Drug Target.Pharmaceuticals (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitochondrial proteostasis, regulated by the mitochondrial unfolded protein response (UPRmt), is crucial for maintenance of cellular functions and survival. Elevated oxidative and proteotoxic stress in mitochondria must be attenuated by the activation of a ubiquitous UPRmt to promote prostate cancer (PCa) growth. Here we show that the 2 key components of the UPRmt, heat shock protein 60 (HSP60, a mitochondrial chaperonin) and caseinolytic protease P (ClpP, a mitochondrial protease), were required for the development of advanced PCa. HSP60 regulated ClpP expression via c-Myc and physically interacted with ClpP to restore mitochondrial functions that promote cancer cell survival. HSP60 maintained the ATP-producing functions of mitochondria, which activated the β-catenin pathway and led to the upregulation of c-Myc. We identified a UPRmt inhibitor that blocked HSP60's interaction with ClpP and abrogated survival signaling without altering HSP60's chaperonin function. Disruption of HSP60-ClpP interaction with the UPRmt inhibitor triggered metabolic stress and impeded PCa-promoting signaling. Treatment with the UPRmt inhibitor or genetic ablation of Hsp60 inhibited PCa growth and progression. Together, our findings demonstrate that the HSP60-ClpP-mediated UPRmt is essential for prostate tumorigenesis and the HSP60-ClpP interaction represents a therapeutic vulnerability in PCa.
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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 Socratic graph.