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

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…

• NS
  National Science Foundation

  Award: 310030
• MF
  McKnight Foundation
• UO
  University of Texas Southwestern Medical Center
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Awards: 130769, 310030, 310030-130769
• UD
  Université de Lausanne
• NI
  National Institutes of Health

  Awards: 5P30 CA142543-03, U54AI057156, 1P01CA95471-09, HHSN268201000044C
• NC
  National Cancer Institute

  Awards: CA109618, HHSN268201000044C, CA142543, 5P30 CA142543