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Updated: Jul 1, 2026

In Vitro Cleavage Assays using Purified Recombinant Drosophila Caspases for Substrate Screening
Published on: October 6, 2022
Effector caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster
Ying-Chen Claire Hou1, Suganthi Chittaranjan, Sharon González Barbosa
1The Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada.
Abstract:
A complex relationship exists between autophagy and apoptosis, but the regulatory mechanisms underlying their interactions are largely unknown. We conducted a systematic study of Drosophila melanogaster cell death-related genes to determine their requirement in the regulation of starvation-induced autophagy. We discovered that six cell death genes--death caspase-1 (Dcp-1), hid, Bruce, Buffy, debcl, and p53-as well as Ras-Raf-mitogen activated protein kinase signaling pathway components had a role in autophagy regulation in D. melanogaster cultured cells. During D. melanogaster oogenesis, we found that autophagy is induced at two nutrient status checkpoints: germarium and mid-oogenesis. At these two stages, the effector caspase Dcp-1 and the inhibitor of apoptosis protein Bruce function to regulate both autophagy and starvation-induced cell death. Mutations in Atg1 and Atg7 resulted in reduced DNA fragmentation in degenerating midstage egg chambers but did not appear to affect nuclear condensation, which indicates that autophagy contributes in part to cell death in the ovary. Our study provides new insights into the molecular mechanisms that coordinately regulate autophagic and apoptotic events in vivo.
Insights
This study reveals that cell death genes and signaling pathways regulate autophagy in Drosophila. Autophagy partially contributes to cell death during oogenesis, highlighting coordinated regulation of cell death and autophagy.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The interplay between autophagy and apoptosis is complex and not fully understood.
- Regulatory mechanisms governing the interaction between these two cell death pathways remain largely unknown.
Purpose of the Study:
- To systematically investigate the role of cell death-related genes in regulating starvation-induced autophagy in Drosophila melanogaster.
- To elucidate the molecular mechanisms coordinating autophagic and apoptotic processes in vivo.
Main Methods:
- Systematic screening of Drosophila melanogaster cell death-related genes.
- Analysis of gene function in cultured D. melanogaster cells and during oogenesis.
- Investigating the impact of mutations in autophagy-related genes (Atg1, Atg7) on cell death markers.
Main Results:
- Six cell death genes (Dcp-1, hid, Bruce, Buffy, debcl, p53) and Ras-Raf-MAPK pathway components regulate autophagy in D. melanogaster cells.
- Autophagy is induced at specific nutrient-dependent checkpoints during oogenesis (germarium and mid-oogenesis).
- The effector caspase Dcp-1 and inhibitor of apoptosis protein Bruce regulate both autophagy and starvation-induced cell death during oogenesis.
- Mutations in Atg1 and Atg7 partially reduced DNA fragmentation in degenerating egg chambers, suggesting autophagy's role in ovarian cell death.
Conclusions:
- Cell death genes and signaling pathways are critical regulators of autophagy in Drosophila.
- Autophagy plays a partial role in ovarian cell death during oogenesis.
- This study provides novel insights into the coordinated regulation of autophagy and apoptosis in vivo.
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