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

Wenting Dai1, Guan Wang1, Jason Chwa1

  • 1Department of Molecular and Cellular Endocrinology, Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.

British Journal of Cancer
|March 10, 2020
PubMed
Abstract

Insights

Mdivi-1, a dynamin-related protein 1 (DRP1) inhibitor, reduces cancer cell oxidative metabolism and proliferation. This effect occurs independently of mitochondrial fusion, suggesting a novel therapeutic strategy for cancer treatment.

Area of Science:

  • Mitochondrial biology
  • Cancer metabolism
  • Cellular respiration

Background:

  • Dynamin-related protein 1 (DRP1) regulates mitochondrial dynamics.
  • Mdivi-1, a DRP1 inhibitor, was previously shown to decrease cancer cell proliferation.
  • The precise metabolic reprogramming induced by DRP1 inhibition in cancer cells remains poorly understood.

Purpose of the Study:

  • To investigate the metabolic effects of DRP1 inhibition by mdivi-1 in various cancer cell lines.
  • To elucidate the role of mitochondrial dynamics in mediating mdivi-1's metabolic impact.

Main Methods:

  • Utilized [U-13C]glucose isotope tracing to analyze metabolic flux.
  • Assessed mdivi-1 effects in DRP1-WT and DRP1-KO H460 lung cancer cells and mouse embryonic fibroblasts (MEFs).
  • Confirmed mitochondrial morphology changes using mitochondrial staining.

Main Results:

  • Mdivi-1 treatment and DRP1 deficiency induced mitochondrial fusion.
  • Metabolic isotope tracing revealed decreased mitochondrial oxidative metabolism in mdivi-1-treated cancer cells (H460, A549, HCT116).
  • TCA cycle intermediates showed significantly lower enrichment in mdivi-1-treated cells, independent of mitochondrial fusion.

Conclusions:

  • Mdivi-1, a DRP1 inhibitor, decreases oxidative metabolism in cancer cells.
  • This reduction in oxidative metabolism contributes to impaired cancer cell proliferation.
  • DRP1 inhibition represents a potential therapeutic avenue for targeting cancer cell metabolism.

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