PT - JOURNAL ARTICLE AU - Zhenyu Zhu AU - Qingsheng Hou AU - Bishi Wang AU - Changhao Li AU - Luguang Liu AU - Weipeng Gong AU - Jie Chai AU - Hongliang Guo AU - Yanhan Jia TI - FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration AID - 10.26508/lsa.202201413 DP - 2022 Nov 01 TA - Life Science Alliance PG - e202201413 VI - 5 IP - 11 4099 - https://www.life-science-alliance.org/content/5/11/e202201413.short 4100 - https://www.life-science-alliance.org/content/5/11/e202201413.full SO - Life Sci. Alliance2022 Nov 01; 5 AB - 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.