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FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration

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机构： [1]Gastrointestinal Surgery Ward II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China [2]Gastrointestinal Surgery Ward I, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China [3]Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China

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Mitochondrial respiration and metabolism play a key role in the pathogenesis and progression of colon adenocarcinoma (COAD). Here, we report a functional pool of FKBP4, a co-chaperone protein, in the mitochondrial intermembrane space (IMS) of colon cancer cells. We found that IMS-localized FKBP4 is essential for the maintenance of mitochondrial respiration, thus contributing to the sensitivity of COAD cells to 5-fluorouracil (5-FU). Mechanistically, FKBP4 interacts with COA6 and controls the assembly of the mitochondrial COA6/SCO1/SCO2 complex, thereby governing COA6-regulated biogenesis and activity of mitochondrial cytochrome c oxidase (complex IV). Thus, our data reveal IMS-localized FKBP4 as a novel regulator of 5-FU sensitivity in COAD, linking mitochondrial respiration to 5-FU sensitivity in COAD.© 2022 Zhu et al.

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大类 | 2 区生物学

小类 | 2 区生物学

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大类 | 2 区生物学

小类 | 2 区生物学

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Q1 BIOLOGY

最新[2023]版：

Q1 BIOLOGY

影响因子： 3.3 最新[2023版] 3.8 最新五年平均 4.4 出版当年[2022版] 4.5 出版当年五年平均 5.781 出版前一年[2021版] 3.3 出版后一年[2023版]

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第一作者机构： [1]Gastrointestinal Surgery Ward II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China

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