Startseite Involvement of mitophagy in cisplatin-induced cell death regulation
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Involvement of mitophagy in cisplatin-induced cell death regulation

  • Alibek Abdrakhmanov , Andrey V. Kulikov , Ekaterina A. Luchkina , Boris Zhivotovsky und Vladimir Gogvadze EMAIL logo
Veröffentlicht/Copyright: 20. Juni 2018

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.

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).

  1. Conflict of interest statement: The authors declare that there is no conflict of interest regarding the publication of this article.

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Received: 2018-04-06
Accepted: 2018-06-14
Published Online: 2018-06-20
Published in Print: 2019-01-28

©2019 Walter de Gruyter GmbH, Berlin/Boston

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