ArticleProceedings of the National Academy of Sciences of the United States of America2013
Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 371 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
371 citing papers in PubMed, 4 syntheses or guidelines pooled it, 568 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Programmed cell death in human respiratory syncytial virus infection.Frontiers in cellular and infection microbiology · 2025Pooled it
- The romantic history of signaling pathway discovery in cell death: an updated review.Molecular and cellular biochemistry · 2024Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Drugging small-molecule compounds in autophagy-dependent cell death to overcome cancer therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Repurposing Antipsychotics in Cancer Therapy: Modulation of Autophagy Mechanisms.Clinical drug investigation · 2026Review
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Photodynamic therapy mediates antitumor effects through multiple non‑apoptotic cell death pathways.Journal of biomedical science · 2026Review
- Review
- Redox-modulation of regulated cell death: implications for synergistic anticancer therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Insights in ischemia/reperfusion injury and cardioprotection: neglected and emerging pathways and therapeutic targets for a personalized therapy.Basic research in cardiology · 2026Review
- The autophagy switch: A critical determinant of arsenic-induced carcinogenesis and cancer therapy.Toxicology reports · 2026Review
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Review
- Article
- MLKL Deficiency Stabilizes RIP3 and Aggravates Myocardial Injury by Promoting Apoptosis and Pyroptosis.Current issues in molecular biology · 2026Article
- Structure-Activity Relationship Studies Enable Optimization of a Small-Molecule Autophagy Activator and Evaluation of Effects on Cell Death Pathways.ACS pharmacology & translational science · 2026Article
- Kremen1 dependence receptor induces SEC24C and ATG9A-dependent cell death.Cell communication and signaling : CCS · 2026Article
311 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 5 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.