Mitochondrial division inhibitor (mdivi-1) decreases oxidative metabolism in cancer.

British Journal of Cancer
Wenting DaiLei Jiang

Abstract

Previous studies suggested that mdivi-1 (mitochondrial division inhibitor), a putative inhibitor of dynamin-related protein (DRP1), decreased cancer cell proliferation through inducing mitochondrial fusion and altering oxygen consumption. However, the metabolic reprogramming underlying the DRP1 inhibition is still unclear in cancer cells. To better understand the metabolic effect of DRP1 inhibition, [U-13C]glucose isotope tracing was employed to assess mdivi-1 effects in several cancer cell lines, DRP1-WT (wild-type) and DRP1-KO (knockout) H460 lung cancer cells and mouse embryonic fibroblasts (MEFs). Mitochondrial staining confirmed that mdivi-1 treatment and DRP1 deficiency induced mitochondrial fusion. Surprisingly, metabolic isotope tracing found that mdivi-1 decreased mitochondrial oxidative metabolism in the lung cancer cell lines H460, A549 and the colon cancer cell line HCT116. [U-13C]glucose tracing studies also showed that the TCA cycle intermediates had significantly lower enrichment in mdivi-1-treated cells. In comparison, DRP1-WT and DRP1-KO H460 cells had similar oxidative metabolism, which was decreased by mdivi-1 treatment. Furthermore, mdivi-1-mediated effects on oxidative metabolism were independent of mitocho...Continue Reading

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Citations

Aug 9, 2020·Cancer Biotherapy & Radiopharmaceuticals·Peiyu HanYiteng Meng
Aug 23, 2020·International Journal of Molecular Sciences·Luca FrattaruoloAnna Rita Cappello
Oct 13, 2020·EMBO Reports·Zhichao WangLei Jiang
Jan 17, 2021·Scientific Reports·Magdalena Gorska-PonikowskaZbigniew Kmiec
May 6, 2021·International Journal of Molecular Sciences·Ilaria GenoveseCarlotta Giorgi
May 22, 2021·Cell Death Discovery·Chieh-Ting FangLing-Huei Yih
Aug 8, 2021·International Journal of Dermatology·Divya Gupta, Tasduq S Abdullah

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Methods Mentioned

BETA
xenograft
GTPase
transfections
flow cytometry
protein assay

Software Mentioned

Prism
Zeiss Zen
Image J
AxioVision
MATLAB

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