Cited by 611Autophagy in Disease and TherapyCell death mechanisms and regulationCalcium signaling and nucleotide metabolism

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

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Liu, Yang, Shoji-Kawata, Sanae, Sumpter, Rhea M., Wei, Yongjie, Ginet, Vanessa, Zhang, Liying, Posner, Bruce, Tran, Khoa A., Green, Douglas R., Xavier, Ramnik J., Shaw, Stanley Y., Clarke, Peter G. H., Puyal, Julien, Levine, Beth·2013·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1319661110PMC PMC3870705

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Abstract

Significance: We show that the selective overactivation of autophagy can cause cell death with unique morphological features distinct from apoptosis or necrosis. This unique type of autophagic cell death, termed “autosis,” occurs not only in vitro but also in vivo in cerebral hypoxia–ischemia. Moreover, autosis is inhibited both in vitro and in vivo by cardiac glycosides, which are Na + ,K + -ATPase antagonists used in clinical medicine. Our findings contribute to the basic understanding of cell-death mechanisms and suggest strategies for protecting cells against stresses such as hypoxia–ischemia.

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Preface
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Authors: 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. H., Puyal, J., & Levine, B.
Affiliations: Center for Autophagy Research,
Howard Hughes Medical Institute (US)
University of Lausanne (CH)
Biochemistry, and
Center for Systems Biology (US)
St. Jude Children's Research Hospital (US)
Broad Institute (US)
ORCID: Liu, Yang
Zhang, Liying
Posner, Bruce
Tran, Khoa A.
Green, Douglas R.
Xavier, Ramnik J.
Shaw, Stanley Y.
Puyal, Julien
Levine, Beth
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2013-11-25
Volume: 110
Issue: 51
Pages: 20364-20371
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1319661110
PMC: PMC3870705
OpenAlex: W2145084709
Cited by: 607
References: 35
Citations by year: 2026: 33 · 2025: 48 · 2024: 38 · 2023: 51 · 2022: 46 · 2021: 58 · 2020: 50 · 2019: 51 · 2018: 43 · 2017: 58 · 2016: 47 · 2015: 43 · 2014: 38
FWCI: 31.15
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
IRIS (submittedVersion)
Funders: National Science Foundation (310030)
Howard Hughes Medical Institute
McKnight Foundation
University of Texas Southwestern Medical Center
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (130769, 310030)
Université de Lausanne
National Institutes of Health (HHSN268201000044C, 5p01ca095471-10, 1P01CA95471-09)
U.S. Public Health Service (R01 A140646)
National Heart, Lung, and Blood Institute (HHSN268201000044C)
National Cancer Institute (P01 CA95471, P01-CA095471, R01CA169291, CA109618, HHSN268201000044C, (CA142543), R01CA109618, P30CA142543)
National Institute of Allergy and Infectious Diseases (R01AI040646, U54AI057156)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords: autophagic cell death, Na+/K+-ATPase, Beclin-1, starvation, hypoxia-ischemia, hippocampal neurons, cardiac glycosides, Na+/K+-ATPase alpha1 subunit, autophagosomes, cell death regulation
MeSH terms: Sodium-Potassium-Exchanging ATPase, Animals, Autophagy, Cardiac Glycosides, Brain Ischemia, HeLa Cells, Humans, Nerve Tissue Proteins, Rats, Cell-Penetrating Peptides

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

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