Abstract
Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. The removal of malfunctioning or damaged mitochondria is essential for normal cellular physiology and tissue development. Stimulation of mitochondrial permeabilization and release of proapoptotic factors from the intermembrane space is an essential step in triggering the mitochondrial pathway of cell death. In this study, we analyzed the extent to which mitophagy interferes with cell death, attenuating the efficiency of cancer therapy. We show that stimulation of mitophagy suppressed cisplatin-induced apoptosis, while mitophagy inhibition stimulates apoptosis and autophagy. Suppression of mitophagy involved production of reactive oxygen species, and the fate of cell was dependent on the interplay between endoplasmic reticulum stress and autophagy.
Funding source: Russian Science Foundation
Award Identifier / Grant number: 14-25-00056
Funding statement: We thank Prof. Bert Vogelstein for HCT116 cells. This work was supported by Russian Science Foundation, Funder Id: 10.13039/501100006769 (grant number 14-25-00056). The work in the authors’ laboratories is being supported by the Stockholm, Funder Id: 10.13039/501100007231 (grant number 161292) and Swedish, Funder Id: 10.13039/501100002794 (grant number 160733) Cancer Societies, the Swedish Childhood Cancer Foundation, Funder Id: 10.13039/501100006313 (grant number PR2016-0090), the Swedish Research Council, Funder Id: 10.13039/501100004359 (grant number 521-2014-2258).
Conflict of interest statement: The authors declare that there is no conflict of interest regarding the publication of this article.
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©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Mitochondria, Apoptosis and Cancer (MAC) 2017
- Transglutaminase type 2 in the regulation of proteostasis
- Mitochondria-driven elimination of cancer and senescent cells
- Comparative study of the differential cell death protecting effect of various ROS scavengers
- Involvement of mitophagy in cisplatin-induced cell death regulation
- Differential involvement of TAK1, RIPK1 and NF-κB signaling in Smac mimetic-induced cell death in breast cancer cells
- Selective BH3-mimetics targeting BCL-2, BCL-XL or MCL-1 induce severe mitochondrial perturbations
- BNIP3 contributes to the glutamine-driven aggressive behavior of melanoma cells
- Review
- Multiple binding sites in organic cation transporters require sophisticated procedures to identify interactions of novel drugs
- Research Articles/Short Communications
- Membranes, Lipids, Glycobiology
- Characterization of the cholesterol efflux of apolipoprotein E-containing high-density lipoprotein in THP-1 cells
- Advanced glycation endproducts and polysialylation affect the turnover of the neural cell adhesion molecule (NCAM) and the receptor for advanced glycation endproducts (RAGE)
- Cell Biology and Signaling
- miR-34a-5p aggravates hypoxia-induced apoptosis by targeting ZEB1 in cardiomyocytes
- MicroRNA-1225-5p acts as a tumor-suppressor in laryngeal cancer via targeting CDC14B
- Novel Techniques
- Tandem DNAzyme for double digestion: a new tool for circRNA suppression
Articles in the same Issue
- Frontmatter
- Mitochondria, Apoptosis and Cancer (MAC) 2017
- Transglutaminase type 2 in the regulation of proteostasis
- Mitochondria-driven elimination of cancer and senescent cells
- Comparative study of the differential cell death protecting effect of various ROS scavengers
- Involvement of mitophagy in cisplatin-induced cell death regulation
- Differential involvement of TAK1, RIPK1 and NF-κB signaling in Smac mimetic-induced cell death in breast cancer cells
- Selective BH3-mimetics targeting BCL-2, BCL-XL or MCL-1 induce severe mitochondrial perturbations
- BNIP3 contributes to the glutamine-driven aggressive behavior of melanoma cells
- Review
- Multiple binding sites in organic cation transporters require sophisticated procedures to identify interactions of novel drugs
- Research Articles/Short Communications
- Membranes, Lipids, Glycobiology
- Characterization of the cholesterol efflux of apolipoprotein E-containing high-density lipoprotein in THP-1 cells
- Advanced glycation endproducts and polysialylation affect the turnover of the neural cell adhesion molecule (NCAM) and the receptor for advanced glycation endproducts (RAGE)
- Cell Biology and Signaling
- miR-34a-5p aggravates hypoxia-induced apoptosis by targeting ZEB1 in cardiomyocytes
- MicroRNA-1225-5p acts as a tumor-suppressor in laryngeal cancer via targeting CDC14B
- Novel Techniques
- Tandem DNAzyme for double digestion: a new tool for circRNA suppression