Mitochondrial ClpX Inhibition Induces Ferroptosis and Blocks Pancreatic Cancer Cell Proliferation
文献类型：期刊论文
| 作者 | Wang, Pengyu1; Zhang, Ranran1; Pan, Yihui1,2; Wu, Wei2,3; Zhang, Tao2,3,4; Yang, Cai-Guang1,2,3,4 |
| 刊名 | CHEMBIOCHEM
 |
| 出版日期 | 2025-09-11 |
| 页码 | 11 |
| 关键词 | ClpX ferroptosis inhibitor mitochondria pancreatic ductal adenocarcinoma |
| ISSN号 | 1439-4227 |
| DOI | 10.1002/cbic.202500551 |
| 英文摘要 | The ATPase caseinolytic protease X (ClpX), forming the ClpXP complex with caseinolytic protease P (ClpP), is essential for mitochondrial protein homeostasis. While ClpP targeting is a recognized anticancer strategy, the role of ClpX in cancer remains underexplored. In pancreatic ductal adenocarcinoma (PDAC), elevated CLPX expression correlates with poor prognosis, suggesting its oncogenic function. CLPX knockdown disrupts mitochondrial homeostasis, and reduces oxidative phosphorylation, thus leading to mitochondrial dysfunction and impaired PDAC cell proliferation. The ClpX-mediated mitochondrial dysfunction induces oxidative stress, unfolded protein response (UPR), and ferroptosis, which is evidenced by increased reactive oxygen species, ferrous iron, lipid peroxidation, and malondialdehyde levels. Screening ATPase inhibitors identifies MSC1094308 as a hit compound for ClpX inhibition, which suppresses ClpXP activity and induces UPR and ferroptosis in PDAC cells. These findings highlight ClpX inhibition as a promising therapeutic strategy for PDAC. |
| WOS关键词 | METABOLISM ; TARGET ; PROTEASE ; PDAC |
| 资助项目 | Youth Innovation Promotion Association of CAS |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001567910600001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321450]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Zhang, Tao; Yang, Cai-Guang |
| 作者单位 | 1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Chem Biol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Pengyu,Zhang, Ranran,Pan, Yihui,et al. Mitochondrial ClpX Inhibition Induces Ferroptosis and Blocks Pancreatic Cancer Cell Proliferation[J]. CHEMBIOCHEM,2025:11. |
| APA | Wang, Pengyu,Zhang, Ranran,Pan, Yihui,Wu, Wei,Zhang, Tao,&Yang, Cai-Guang.(2025).Mitochondrial ClpX Inhibition Induces Ferroptosis and Blocks Pancreatic Cancer Cell Proliferation.CHEMBIOCHEM,11. |
| MLA | Wang, Pengyu,et al."Mitochondrial ClpX Inhibition Induces Ferroptosis and Blocks Pancreatic Cancer Cell Proliferation".CHEMBIOCHEM (2025):11. |
入库方式： OAI收割
来源：上海药物研究所
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