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Zein L, Fulda S, Kögel D, et al. Organelle-specific mechanisms of drug-induced autophagy-dependent cell death. Matrix Biol. 2020;100:54-64doi: 10.1016/j.matbio.2020.12.003.
Zein, L., Fulda, S., Kögel, D., & van Wijk, S. J. L. (2021). Organelle-specific mechanisms of drug-induced autophagy-dependent cell death. Matrix biology : journal of the International Society for Matrix Biology, 10054-64. https://doi.org/10.1016/j.matbio.2020.12.003
Zein, Laura, et al. "Organelle-specific mechanisms of drug-induced autophagy-dependent cell death." Matrix biology : journal of the International Society for Matrix Biology vol. 100 (2021): 54-64. doi: https://doi.org/10.1016/j.matbio.2020.12.003
Zein L, Fulda S, Kögel D, van Wijk SJL. Organelle-specific mechanisms of drug-induced autophagy-dependent cell death. Matrix Biol. 2021 Jun;100:54-64. doi: 10.1016/j.matbio.2020.12.003. Epub 2020 Dec 13. PMID: 33321172.
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Matrix Biol. 2021 Jun;100:54-64. doi: 10.1016/j.matbio.2020.12.003. Epub 2020 Dec 13.

Organelle-specific mechanisms of drug-induced autophagy-dependent cell death.

Matrix biology : journal of the International Society for Matrix Biology

Laura Zein, Simone Fulda, Donat Kögel, Sjoerd J L van Wijk

Affiliations

  1. Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstrasse 3a, 60528 Frankfurt am Main, Germany.
  2. Experimental Neurosurgery, Goethe-University Hospital, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt, Germany.
  3. Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Komturstrasse 3a, 60528 Frankfurt am Main, Germany. Electronic address: [email protected].

PMID: 33321172 DOI: 10.1016/j.matbio.2020.12.003

Abstract

The conserved catabolic process of autophagy is an important control mechanism that degrades cellular organelles, debris and pathogens in autolysosomes. Although autophagy primarily protects against cellular insults, nutrient starvation or oxidative stress, hyper-activation of autophagy is also believed to cause autophagy-dependent cell death (ADCD). ADCD is a caspase-independent form of programmed cell death (PCD), characterized by an over-activation of autophagy, leading to prominent self-digestion of cellular material in autolysosomes beyond the point of cell survival. ADCD plays important roles in the development of lower organisms, but also in the response of cancer cells upon exposure of specific drugs or natural compounds. Importantly, the induction of ADCD as an alternative cell death pathway is of special interest in apoptosis-resistant cancer types and serves as an attractive and potential therapeutic option. Although the mechanisms of ADCD are diverse and not yet fully understood, both non-selective (bulk) autophagy and organelle-specific types of autophagy are believed to be involved in this type of cell death. Accordingly, several ADCD-inducing drugs are known to trigger severe mitochondrial damage and endoplasmic reticulum (ER) stress, whereas the contribution of other cell organelles, like ribosomes or peroxisomes, to the control of ADCD is not well understood. In this review, we highlight the general mechanisms of ADCD and discuss the current evidence for mitochondria- and ER-specific killing mechanisms of ADCD-inducing drugs.

Copyright © 2020 Elsevier B.V. All rights reserved.

Keywords: Autophagy-dependent cell death; ER, ER stress; Mitochondria; Mitophagy

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