Autophagic degradation of dBruce controls DNA fragmentation in nurse cells during late Drosophila melanogaster oogenesis.
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.
Nezis
Ioannis P
IP
Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Ioannis.Nezis@rr-research.no
Shravage
Bhupendra V
BV
Sagona
Antonia P
AP
Lamark
Trond
T
Bjørkøy
Geir
G
Johansen
Terje
T
Rusten
Tor Erik
TE
Brech
Andreas
A
Baehrecke
Eric H
EH
Stenmark
Harald
H
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
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