title: Cell death during Drosophila melanogaster early oogenesis is mediated through autophagy.
abstract: Autophagy is a physiological and evolutionarily conserved process maintaining homeostatic functions, such as protein degradation and organelle turnover. Accumulating data provide evidence that autophagy also contributes to cell death under certain circumstances, but how this is achieved is not well known. Herein, we report that autophagy occurs during developmentally-induced cell death in the female germline, observed in the germarium and during middle developmental stages of oogenesis in Drosophila melanogaster. Degenerating germline cells exhibit caspase activation, chromatin condensation, DNA fragmentation and punctate staining of mCherry-DrAtg8a, a novel marker for monitoring autophagy in Drosophila. Genetic inhibition of autophagy, by removing atg1 or atg7 function, results in significant reduction of DNA fragmentation, suggesting that autophagy acts genetically upstream of DNA fragmentation in this tissue. This study provides new insights into the mechanisms that regulate cell death in vivo during development.
authors.affiliation: Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, Department of Biochemistry, Rikshospitalet-Radiumhospitalet HF, Montebello, Oslo, Norway.
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Nezis
authors.forename: Trond
authors.initials: T
authors.lastname: Lamark
authors.forename: Athanassios D
authors.initials: AD
authors.lastname: Velentzas
authors.forename: Tor Erik
authors.initials: TE
authors.lastname: Rusten
authors.forename: Geir
authors.initials: G
authors.lastname: Bjørkøy
authors.forename: Terje
authors.initials: T
authors.lastname: Johansen
authors.forename: Issidora S
authors.initials: IS
authors.lastname: Papassideri
authors.forename: Dimitrios J
authors.initials: DJ
authors.lastname: Stravopodis
authors.forename: Lukas H
authors.initials: LH
authors.lastname: Margaritis
authors.forename: Harald
authors.initials: H
authors.lastname: Stenmark
authors.forename: Andreas
authors.initials: A
authors.lastname: Brech
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D000071189:Autophagy-Related Protein-1 Homolog; D020169:Caspases / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D053938:DNA Fragmentation; D015509:Developmental Biology; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D005260:Female; D005854:Germ Cells / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D008957:Models, Genetic; D009866:Oogenesis / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics
chemical_list: C530193:Atg7 protein, Drosophila; D002843:Chromatin; D029721:Drosophila Proteins; C518074:Atg1 protein, Drosophila; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; D020169:Caspases; D000071193:Autophagy-Related Protein 7