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

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...

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Autores principales: Zhu, Zhenyu, Hou, Qingsheng, Wang, Bishi, Li, Changhao, Liu, Luguang, Gong, Weipeng, Chai, Jie, Guo, Hongliang, Jia, Yanhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389594/
https://www.ncbi.nlm.nih.gov/pubmed/35981890
http://dx.doi.org/10.26508/lsa.202201413
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author Zhu, Zhenyu
Hou, Qingsheng
Wang, Bishi
Li, Changhao
Liu, Luguang
Gong, Weipeng
Chai, Jie
Guo, Hongliang
Jia, Yanhan
author_facet Zhu, Zhenyu
Hou, Qingsheng
Wang, Bishi
Li, Changhao
Liu, Luguang
Gong, Weipeng
Chai, Jie
Guo, Hongliang
Jia, Yanhan
author_sort Zhu, Zhenyu
collection PubMed
description 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.
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spelling pubmed-93895942022-09-02 FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration Zhu, Zhenyu Hou, Qingsheng Wang, Bishi Li, Changhao Liu, Luguang Gong, Weipeng Chai, Jie Guo, Hongliang Jia, Yanhan Life Sci Alliance Research Articles 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. Life Science Alliance LLC 2022-08-18 /pmc/articles/PMC9389594/ /pubmed/35981890 http://dx.doi.org/10.26508/lsa.202201413 Text en © 2022 Zhu et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Zhu, Zhenyu
Hou, Qingsheng
Wang, Bishi
Li, Changhao
Liu, Luguang
Gong, Weipeng
Chai, Jie
Guo, Hongliang
Jia, Yanhan
FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
title FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
title_full FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
title_fullStr FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
title_full_unstemmed FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
title_short FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
title_sort fkbp4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389594/
https://www.ncbi.nlm.nih.gov/pubmed/35981890
http://dx.doi.org/10.26508/lsa.202201413
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