title: Autophagic degradation of dBruce controls DNA fragmentation in nurse cells during late Drosophila melanogaster oogenesis.
abstract: Autophagy is an evolutionarily conserved pathway responsible for degradation of cytoplasmic material via the lysosome. Although autophagy has been reported to contribute to cell death, the underlying mechanisms remain largely unknown. In this study, we show that autophagy controls DNA fragmentation during late oogenesis in Drosophila melanogaster. Inhibition of autophagy by genetically removing the function of the autophagy genes atg1, atg13, and vps34 resulted in late stage egg chambers that contained persisting nurse cell nuclei without fragmented DNA and attenuation of caspase-3 cleavage. The Drosophila inhibitor of apoptosis (IAP) dBruce was found to colocalize with the autophagic marker GFP-Atg8a and accumulated in autophagy mutants. Nurse cells lacking Atg1 or Vps34 in addition to dBruce contained persisting nurse cell nuclei with fragmented DNA. This indicates that autophagic degradation of dBruce controls DNA fragmentation in nurse cells. Our results reveal autophagic degradation of an IAP as a novel mechanism of triggering cell death and thereby provide a mechanistic link between autophagy and cell death.
authors: Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Ioannis.Nezis@rr-research.no
authors: Ioannis P
authors: IP
authors: Nezis
authors: Bhupendra V
authors: BV
authors: Shravage
authors: Antonia P
authors: AP
authors: Sagona
authors: Trond
authors: T
authors: Lamark
authors: Geir
authors: G
authors: Bjørkøy
authors: Terje
authors: T
authors: Johansen
authors: Tor Erik
authors: TE
authors: Rusten
authors: Andreas
authors: A
authors: Brech
authors: Eric H
authors: EH
authors: Baehrecke
authors: Harald
authors: H
authors: Stenmark
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071189:Autophagy-Related Protein-1 Homolog; D000071183:Autophagy-Related Proteins; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D053938:DNA Fragmentation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000502:physiology*; D005260:Female; D009866:Oogenesis / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
chemical_list: D000071189:Autophagy-Related Protein-1 Homolog; D000071183:Autophagy-Related Proteins; D053148:Caspase 3; D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; C541704:Atg13 protein, Drosophila; C527373:Atg8a protein, Drosophila; C470733:Bruce protein, Drosophila; C518074:Atg1 protein, Drosophila