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Mitochondrial Protease ClpP: Cancer Marker and Drug Target
Domenico Armenise1, Olga Maria Baldelli1, Anselma Liturri1
1Research Laboratory for Woman and Child Health, Department of Pharmacy-Pharmaceutical Sciences, University of Bari "Aldo Moro", Via E. Orabona 4, 70125 Bari, Italy.
Pharmaceuticals (Basel, Switzerland)
|October 29, 2025
Summary
The mitochondrial ClpP protease is upregulated in tumors and crucial for cancer cell survival. Modulating its activity offers a promising therapeutic strategy for precision oncology.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Human mitochondrial ClpP is a matrix-localized serine protease vital for protein homeostasis.
- Dysregulation of proteostasis, including ClpP function, is implicated in cancer progression.
Purpose of the Study:
- To review the literature on ClpP's role in cancer.
- To explore ClpP as a potential therapeutic target in oncology.
Main Methods:
- Literature review from 2020-2025 using PubMed and Scopus.
- Focused on ClpP structure, function, activity modulation, and cancer relevance.
- Keywords: "ClpP", "ClpP activators", "ClpP inhibitors", "mitochondrial protease".
Main Results:
- ClpP is frequently upregulated in various tumors compared to normal tissues.
- Cancer cells rely on ClpP for mitochondrial proteostasis, metabolic adaptation, and survival.
- Modulating ClpP activity (activators/inhibitors) disrupts cancer cell processes and shows clinical efficacy.
Conclusions:
- ClpP is a significant factor in cancer pathophysiology.
- Its selective overexpression in tumors and role in mitochondrial homeostasis position it as a key therapeutic target for precision oncology.
Keywords:
ClpP activators/inhibitorsClpP overexpressioncancerhuman ClpP proteasemitochondrial proteostasisquality control systemMore Related Videos
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