Autophagy occurs upstream or parallel to the apoptosome during histolytic cell death

Fatih Akdemir, Robert Farkaš, Po Chen, Gabor Juhasz, Lucia Medved'ova, Miklos Sass, Lai Wang, Xiaodong Wang, Suganthi Chittaranjan, Sharon M. Gorski, Antony Rodriguez, John M. Abrams

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Histolysis refers to a widespread disintegration of tissues that is morphologically distinct from apoptosis and often associated with the stimulation of autophagy. Here, we establish that a component of the apoptosome, and pivotal regulator of apoptosis, is also required for histolytic cell death. Using in vivo and ex vivo assays, we demonstrate a global apoptogenic requirement for dark, the fly ortholog of Apaf1, and show that a required focus of dark- organismal lethality maps to the central nervous system. We further demonstrate that the Dark protein itself is a caspase substrate and find that alterations of this cleavage site produced the first hypermorphic point mutation within the Apaf1/ Ced-4 gene family. In a model of 'autophagic cell death', dark was essential for histolysis but dispensable for characteristic features of the autophagic program, indicating that the induction of autophagy occurs upstream or parallel to histolytic cell death. These results demonstrate that stimulation of autophagy per se is not a 'killing event' and, at the same time, establish that common effector pathways, regulated by the apoptosome, can underlie morphologically distinct forms of programmed cell death.

Original languageEnglish (US)
Pages (from-to)1457-1465
Number of pages9
JournalDevelopment
Volume133
Issue number8
DOIs
StatePublished - Apr 2006

Keywords

  • Apoptosis
  • Autophagy
  • Dark
  • Drosophila
  • Histolysis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Akdemir, F., Farkaš, R., Chen, P., Juhasz, G., Medved'ova, L., Sass, M., Wang, L., Wang, X., Chittaranjan, S., Gorski, S. M., Rodriguez, A., & Abrams, J. M. (2006). Autophagy occurs upstream or parallel to the apoptosome during histolytic cell death. Development, 133(8), 1457-1465. https://doi.org/10.1242/dev.02332