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

Author:

Zhu Zhenyu1,Hou Qingsheng1,Wang Bishi1,Li Changhao1,Liu Luguang1,Gong Weipeng1,Chai Jie2,Guo Hongliang1,Jia Yanhan3ORCID

Affiliation:

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

Abstract

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.

Funder

Shandong Province Major Science and Technology Innovation Project

Publisher

Life Science Alliance, LLC

Subject

Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology

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