Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets
Cells must eliminate excess or damaged proteins to maintain protein homeostasis. To ensure protein homeostasis in the cytoplasm, cells rely on the ubiquitin-proteasome system and autophagy. In the mitochondria, protein homeostasis is regulated by mitochondria proteases, including four core ATP-depen...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/9/2020 |
| _version_ | 1797536764517154816 |
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| author | Yue Feng Kazem Nouri Aaron D. Schimmer |
| author_facet | Yue Feng Kazem Nouri Aaron D. Schimmer |
| author_sort | Yue Feng |
| collection | DOAJ |
| description | Cells must eliminate excess or damaged proteins to maintain protein homeostasis. To ensure protein homeostasis in the cytoplasm, cells rely on the ubiquitin-proteasome system and autophagy. In the mitochondria, protein homeostasis is regulated by mitochondria proteases, including four core ATP-dependent proteases, m-AAA, i-AAA, LonP, and ClpXP, located in the mitochondrial membrane and matrix. This review will discuss the function of mitochondrial proteases, with a focus on ClpXP as a novel therapeutic target for the treatment of malignancy. ClpXP maintains the integrity of the mitochondrial respiratory chain and regulates metabolism by degrading damaged and misfolded mitochondrial proteins. Inhibiting ClpXP genetically or chemically impairs oxidative phosphorylation and is toxic to malignant cells with high ClpXP expression. Likewise, hyperactivating the protease leads to increased degradation of ClpXP substrates and kills cancer cells. Thus, targeting ClpXP through inhibition or hyperactivation may be novel approaches for patients with malignancy. |
| first_indexed | 2024-03-10T12:04:26Z |
| format | Article |
| id | doaj.art-1b71344efef2492f9bfd41928b751283 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:04:26Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1b71344efef2492f9bfd41928b7512832023-11-21T16:38:33ZengMDPI AGCancers2072-66942021-04-01139202010.3390/cancers13092020Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer TargetsYue Feng0Kazem Nouri1Aaron D. Schimmer2Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, CanadaCells must eliminate excess or damaged proteins to maintain protein homeostasis. To ensure protein homeostasis in the cytoplasm, cells rely on the ubiquitin-proteasome system and autophagy. In the mitochondria, protein homeostasis is regulated by mitochondria proteases, including four core ATP-dependent proteases, m-AAA, i-AAA, LonP, and ClpXP, located in the mitochondrial membrane and matrix. This review will discuss the function of mitochondrial proteases, with a focus on ClpXP as a novel therapeutic target for the treatment of malignancy. ClpXP maintains the integrity of the mitochondrial respiratory chain and regulates metabolism by degrading damaged and misfolded mitochondrial proteins. Inhibiting ClpXP genetically or chemically impairs oxidative phosphorylation and is toxic to malignant cells with high ClpXP expression. Likewise, hyperactivating the protease leads to increased degradation of ClpXP substrates and kills cancer cells. Thus, targeting ClpXP through inhibition or hyperactivation may be novel approaches for patients with malignancy.https://www.mdpi.com/2072-6694/13/9/2020mitochondriacancerproteaseClpXPAML |
| spellingShingle | Yue Feng Kazem Nouri Aaron D. Schimmer Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets Cancers mitochondria cancer protease ClpXP AML |
| title | Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets |
| title_full | Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets |
| title_fullStr | Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets |
| title_full_unstemmed | Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets |
| title_short | Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets |
| title_sort | mitochondrial atp dependent proteases biological function and potential anti cancer targets |
| topic | mitochondria cancer protease ClpXP AML |
| url | https://www.mdpi.com/2072-6694/13/9/2020 |
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