title: Autophagy, not apoptosis, is essential for midgut cell death in Drosophila.
abstract: Most developmentally programmed cell death in metazoans is mediated by caspases. During Drosophila metamorphosis, obsolete tissues, including the midgut and salivary glands, are removed by programmed cell death [1]. The initiator caspase Dronc and its activator Ark are required for the death of salivary glands, but not for midgut removal [2, 3]. In addition to caspases, complete removal of salivary glands requires autophagy [4]. However, the contribution of autophagy to midgut cell death has not been explored. Examination of combined mutants of the main initiator and effector caspases revealed that the canonical apoptotic pathway is not required for midgut cell death. Further analyses revealed that the caspase Decay is responsible for most of the caspase activity in dying midguts, yet inhibition of this activity has no effect on midgut removal. By contrast, midgut degradation was severely delayed by inhibition of autophagy, and this occurred without a decrease in caspase activity. Surprisingly, the combined inhibition of caspases and autophagy did not result in an additional delay in midgut removal. Together, our results indicate that autophagy, not caspases, is essential for midgut programmed cell death, providing the first in vivo evidence of caspase-independent programmed cell death that requires autophagy despite the presence of high caspase activity.
authors.affiliation: Department of Haematology, Centre for Cancer Biology, Adelaide, SA, Australia.
authors.forename: Donna
authors.initials: D
authors.lastname: Denton
authors.forename: Bhupendra
authors.initials: B
authors.lastname: Shravage
authors.forename: Rachel
authors.initials: R
authors.lastname: Simin
authors.forename: Kathryn
authors.initials: K
authors.lastname: Mills
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Berry
authors.forename: Eric H
authors.initials: EH
authors.lastname: Baehrecke
authors.forename: Sharad
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000166:cytology* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D008675:Metamorphosis, Biological / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D020169:Caspases; C400190:decay protein, Drosophila