Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia.

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Serval ID
serval:BIB_6167D2A88829
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Liu Y., Shoji-Kawata S., Sumpter R.M., Wei Y., Ginet V., Zhang L., Posner B., Tran K.A., Green D.R., Xavier R.J., Shaw S.Y., Clarke P.G., Puyal J., Levine B.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
110
Number
51
Pages
20364-20371
Language
english
Abstract
A long-standing controversy is whether autophagy is a bona fide cause of mammalian cell death. We used a cell-penetrating autophagy-inducing peptide, Tat-Beclin 1, derived from the autophagy protein Beclin 1, to investigate whether high levels of autophagy result in cell death by autophagy. Here we show that Tat-Beclin 1 induces dose-dependent death that is blocked by pharmacological or genetic inhibition of autophagy, but not of apoptosis or necroptosis. This death, termed "autosis," has unique morphological features, including increased autophagosomes/autolysosomes and nuclear convolution at early stages, and focal swelling of the perinuclear space at late stages. We also observed autotic death in cells during stress conditions, including in a subpopulation of nutrient-starved cells in vitro and in hippocampal neurons of neonatal rats subjected to cerebral hypoxia-ischemia in vivo. A chemical screen of ~5,000 known bioactive compounds revealed that cardiac glycosides, antagonists of Na(+),K(+)-ATPase, inhibit autotic cell death in vitro and in vivo. Furthermore, genetic knockdown of the Na(+),K(+)-ATPase α1 subunit blocks peptide and starvation-induced autosis in vitro. Thus, we have identified a unique form of autophagy-dependent cell death, a Food and Drug Administration-approved class of compounds that inhibit such death, and a crucial role for Na(+),K(+)-ATPase in its regulation. These findings have implications for understanding how cells die during certain stress conditions and how such cell death might be prevented.
Keywords
Animals, Autophagy/drug effects, Brain Ischemia/metabolism, Brain Ischemia/pathology, Cardiac Glycosides/pharmacology, Cell-Penetrating Peptides/pharmacology, HeLa Cells, Humans, Nerve Tissue Proteins/metabolism, Rats, Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors, Sodium-Potassium-Exchanging ATPase/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
20/12/2013 14:32
Last modification date
20/08/2019 15:18
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