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Citation
Akdemir, F., Farkas, 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.
FlyBase ID
FBrf0194101
Publication Type
Research paper
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.

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PubMed Central ID
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Secondary IDs
  • FBrf0198608
Language of Publication
English
Additional Languages of Abstract
Parent Publication
Publication Type
Journal
Abbreviation
Development
Title
Development
Publication Year
1987-
ISBN/ISSN
0950-1991
Data From Reference
Alleles (11)
Genes (8)
Natural transposons (1)
Insertions (3)
Experimental Tools (3)
Transgenic Constructs (5)