Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogaster
Abstract Autophagy-dependent cell death (ADCD) is a context-specific form of programmed cell death that plays an important role in development and homeostasis. During Drosophila metamorphosis, hormonal cues modulate growth and other signalling cascades which results in autophagy-dependent degradatio...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-04-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02474-0 |
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| Summary: | Abstract Autophagy-dependent cell death (ADCD) is a context-specific form of programmed cell death that plays an important role in development and homeostasis. During Drosophila metamorphosis, hormonal cues modulate growth and other signalling cascades which results in autophagy-dependent degradation of the obsolete larval midgut. While this process does not require caspase activity or apoptotic machinery, several canonical autophagy-related proteins are also dispensable, suggesting additional regulators may be involved in effectively eliminating the larval midgut. Ubiquitination, a process that attaches one or more ubiquitin moieties to a substrate through sequential reactions involving a cascade of enzymes, plays a critical role in autophagy. As the specific role(s) of ubiquitination in ADCD has not been explored, we previously performed a RNAi-mediated knockdown screen of over 250 ubiquitin machinery genes in GFP-labelled Drosophila larval midguts and identified 18 candidate regulators of midgut degradation. In this work, we screened candidate genes for a role in autophagy-dependent midgut degradation by analysing mosaic clones and genetic interactions with Atg1. Validation and further studies into the ubiquitin conjugating enzyme, Effete (Eff), and two ubiquitin ligases, Cullin-4 (Cul4) and Supernumerary limbs (Slmb), demonstrated interplay between ubiquitination and the autophagy machinery in coordinating autophagy-dependent midgut degradation. |
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| ISSN: | 2058-7716 |