RT Journal Article
SR Electronic
T1 FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201413
DO 10.26508/lsa.202201413
VO 5
IS 11
A1 Zhenyu Zhu
A1 Qingsheng Hou
A1 Bishi Wang
A1 Changhao Li
A1 Luguang Liu
A1 Weipeng Gong
A1 Jie Chai
A1 Hongliang Guo
A1 Yanhan Jia
YR 2022
UL https://www.life-science-alliance.org/content/5/11/e202201413.abstract
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.