Mitochondrial dynamics regulates hypoxia-induced migration and antineoplastic activity of cisplatin in breast cancer cells

Mitochondria are high dynamic organelles with frequent fission and fusion. Here, we found hypoxia stimulated Drpl expression, mitochondrial fission and migration in metastatic MDA-MB-231 cells, but not in non-metastatic MCF-7 cells. Inhibition of Drpl-dependent mitochondrial fission by Mdivi-1 or silencing Drpl attenuated hypoxia-induced mitochondrial fission and migration in MDA-MB-231 cells. On the other hand, cisplatin induced significant apoptosis and mitochondrial fission in MDA-MB-231 cells, but not in MCF-7 cells. Mdivi-1 and silencing Drpl also efficiently prevented cisplatin-induced MMP decrease, ROS production and apoptosis in MDA-MB-231 cells. Our data suggest that Drpl-dependent mitochondrial fission not only regulates hypoxia-induced migration of breast cancer cells, but also facilitates its sensitivity to chemotherapeutic agents. Thus, targeting Drpl-dependent mitochondrial dynamics may provide a novel strategy to suppress breast cancer metastasis and improve the chemotherapeutic effect in the future.