The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Autosis is a Na + ,K + -ATPase–regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia–ischemia
Open accessAbstract
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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In the citing paper
“Corroborating the physiological relevance of this process, the administration of Na+/K+-ATPase inhibitors such as cardiac glycosides, confers neuroprotection in a rat model of neonatal hypoxia-ischemia [851].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [851]
In the citing paper
“Autosis is a specific variant of autophagy-dependent cell death that relies on the plasma membrane Na+/K+-ATPase [851].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [851]
In the citing paper
“On the one hand, RCD constitutes a primary etiological determinant in diseases associated with the irreversible loss of post-mitotic tissues (e.g., myocardial infarction, neurodegeneration) [687, 752, 851, 869, 1035, 1036].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [851]
In the citing paper
“We found that GC reduced the autophagic gene expression including key genes associated with autophagy induction, such as Atg7 and Beclin 1[45], by 1-5 folds”
From Prevention of glucocorticoid induced bone changes with beta-ecdysone (2015) · cites this paper as [45]
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Citations
Cites
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069
Self-citationGalluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2011.96 · Cited by 2,421
Self-citationDevelopmental cell death: morphological diversity and multiple mechanisms
Clarke, P. H. (1990) · Anatomy and Embryology · doi:10.1007/bf00174615 · Cited by 1,695
Self-citationAutophagy in cell death: an innocent convict?
Levine, B. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26390 · Cited by 1,694
Self-citationMatsui, Y., Takagi, H., Qu, X., Abdellatif, M., Sakoda, H., Asano, T., Levine, B., & Sadoshima, J. (2007) · Circulation Research · doi:10.1161/01.res.0000261924.76669.36 · Cited by 1,505
Self-citationIdentification of a candidate therapeutic autophagy-inducing peptide
Shoji-Kawata, S., Sumpter, R., Leveno, M., Campbell, G. R., Zou, Z., Kinch, L., Wilkins, A. D., Sun, Q., Pallauf, K., MacDuff, D., et al. (2013) · Nature · doi:10.1038/nature11866 · Cited by 760
Self-citationApoptosis, autophagy, and more
Lockshin, R. A., & Zakeri, Z. F. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.04.011 · Cited by 713
Novel therapeutic applications of cardiac glycosides
Prassas, I., & Diamandis, E. P. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2682 · Cited by 673
Cardiac Glycosides as Novel Cancer Therapeutic Agents
Newman, R. A., Yang, P., Pawlus, A. D., & Block, K. I. (2008) · Molecular Interventions · doi:10.1124/mi.8.1.8 · Cited by 517
Mechanisms of Autophagosome Biogenesis
Rubinsztein, D. C., Shpilka, T., & Elazar, Z. (2012) · Current Biology · doi:10.1016/j.cub.2011.11.034 · Cited by 517
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Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets
Li, T., Zhang, Q., Wu, Y., & Huang, R. (2026) · MedComm · doi:10.1002/mco2.70915
Targeting autophagy-dependent cell death in cancer therapy: An update on small-molecule compounds
Yang, Y., Chen, M., Xie, Q., Cheng, L., & Liu, B. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110434
Zhao, R., Zhao, J., 殷洪年, Zhan, Y., Ma, D., Xu, X., & Yang, W. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1876124
“Autosis provides an experimentally defined example of cell death that is dependent on the autophagic machinery and regulated by Na+,K + -ATPase (Liu et al., 2013); however, broader claims of autophagy-dependent cell death should require pathway-specific evidence that disruption of the essential…”
Peng, Z., Pei, X., Gao, R., Wu, D., & Liu, B. (2026) · APOPTOSIS · doi:10.1007/s10495-026-02437-5
Chen, S., Liu, Y., Bao, H., Zhao, E., Qiao, X., Gu, M., ZHOU, J., & Zhang, J. (2026) · International Journal of Radiation Research · doi:10.66224/ijrr.24.3.18
Self-citationMetabolic hallmarks of regulated cell death
Kang, R., Chen, X., Kroemer, G., & Tang, D. (2026) · Cell Research · doi:10.1038/s41422-026-01306-9
Uversky, V. N. (2026) · Biochemistry (Moscow) · doi:10.1134/s0006297926601656
Erebosis: An Emerging Concept of a New Type of Regulated Cell Death
Nikulin, S. V., Hushpulian, D. M., Zakharyants, A. A., Thomas, B., Kazakov, S. V., & Gazaryan, I. G. (2026) · Biochemistry (Moscow) · doi:10.1134/s0006297926602935
Mechanisms and pharmacological modulation of photodynamic therapy-induced cell death
de Klerk, D. J., Tian, J., Liu, G., Korbelik, M., Kessel, D., Chovanec, M., Khaled, Y. S., van Eijck, C. H. J., Wu, L., & Heger, M. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100166
A guide to autophagy-dependent cell death: concepts, criteria, and mechanisms
Meng, L., Dai, M., Zhang, X., Kang, R., Tang, D., Liu, N., Guan, L., & Han, L. (2026) · Autophagy · doi:10.1080/15548627.2026.2753812
Metadata
- 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
- 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
- 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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