ArticleBiochimica et biophysica acta2016
Mitochondrial ClpP activity is required for cisplatin resistance in human cells.
Article in Biochimica et biophysica acta, 2016. 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- CDH11 Contributes to Bladder Cancer Progression via Regulation of Mitochondrial Energy Metabolism.Cancer medicine · 2025Article
- Recent advances in the design of small molecules targeting human ClpP.Future medicinal chemistry · 2025Review
- TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells.Molecular cancer therapeutics · 2024Article
- Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer.Journal of translational medicine · 2024Review
- A bird's eye view of mitochondrial unfolded protein response in cancer: mechanisms, progression and further applications.Cell death & disease · 2024Review
- Review
- The crosstalk between mitochondrial quality control and metal-dependent cell death.Cell death & disease · 2024Review
- Targeting Cancer Mitochondria by Inducing an Abnormal Mitochondrial Unfolded Protein Response Leads to Tumor Suppression.International journal of medical sciences · 2024Article
- The mitochondrial unfolded protein response (UPRJournal of hematology & oncology · 2022Review
- A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60.The Journal of clinical investigation · 2022Article
- Lon upregulation contributes to cisplatin resistance by triggering NCLX-mediated mitochondrial CaCell death & disease · 2022Article
- Insight into the mitochondrial unfolded protein response and cancer: opportunities and challenges.Cell & bioscience · 2022Review
- Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- Mitochondrial ClpP serine protease-biological function and emerging target for cancer therapy.Cell death & disease · 2020Review
- Methyl-Cantharidimide (MCA) Has Anticancer Efficacy in ABCB1- and ABCG2-Overexpressing and Cisplatin Resistant Cancer Cells.Frontiers in oncology · 2020Article
- Mitochondrial Involvement in Cisplatin Resistance.International journal of molecular sciences · 2019Review
- ClpP Protease, a Promising Antimicrobial Target.International journal of molecular sciences · 2019Review
- Mitochondrial miRNA Determines Chemoresistance by Reprogramming Metabolism and Regulating Mitochondrial Transcription.Cancer research · 2019Article
- Decreased expression of mitochondrial miR-5787 contributes to chemoresistance by reprogramming glucose metabolism and inhibiting MT-CO3 translation.Theranostics · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In human cells ClpP and ClpX are imported into the mitochondrial matrix, where they interact to form the ATP-dependent protease ClpXP and play a role in the mitochondrial unfolded protein response. We find that reducing the levels of mitochondrial ClpP or ClpX renders human cancer cells more sensitive to cisplatin, a widely used anti-cancer drug. Conversely, overexpression of HClpP desensitizes cells to cisplatin. Overexpression of inactive HClpP-S97A had no effect. Cisplatin resistance correlated with decreased cellular accumulation of cisplatin and decreased levels of diguanosine-cisplatin adducts in both mitochondrial and genomic DNA. In contrast, higher levels of cisplatin-DNA adducts were found in cells in which HClpP had been depleted. Changes in the levels of ClpP had no effect on the levels of CTR1, a copper transporter that contributes to cisplatin uptake. However, the levels of ATP7A and ATP7B, copper efflux pumps that help eliminate cisplatin from cells, were increased when HClpP was overexpressed. HClpP levels were elevated in cervical carcinoma cells (KB-CP20) and hepatoma cells (BEL-7404-CP20) independently selected for cisplatin resistance. The data indicate that robust HClpXP activity positively affects the ability of cells to efflux cisplatin and suggest that targeting HClpP or HClpX would offer a novel mechanism for sensitizing cancer cells to cisplatin.
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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.