Co-targeting Mitochondrial Ca²⁺ Homeostasis and Autophagy Enhances Cancer Cells' Chemosensitivity.

ABSTRACT: Mitochondria are important cell death checkpoints, and mitochondrial Ca²⁺ overload is considered as a potent apoptotic intrinsic pathway inducer. Here, we report that this Ca²⁺ apoptosis link is largely ineffective in inducing cell-death just by itself and required a concomitant inhibition of autophagy to counteract its pro-survival action. In such condition, an acute mitochondrial stress revealed by a DRP1-mediated mitochondrial dynamic remodeling is observed concomitantly with mitochondrial depolarization, release of cytochrome c, and efficient apoptosis induction. We also uncover that mitochondrial Ca²⁺ status modulates the function of autophagy as a sensitizer for chemotherapies. This priming mediated by mitochondrial Ca²⁺ overload and inhibi

SUBMITTER: Dubois C 

PROVIDER: S-EPMC7322071 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature