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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| Format: | Article |
| Language: | English |
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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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| author | Ruchi Umargamwala Shannon Nicolson Jantina Manning Julian M. Carosi Sharad Kumar Donna Denton |
| author_facet | Ruchi Umargamwala Shannon Nicolson Jantina Manning Julian M. Carosi Sharad Kumar Donna Denton |
| author_sort | Ruchi Umargamwala |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c30fdd3cc6a847cd921f06d2f1fb0d01 |
| institution | OA Journals |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-c30fdd3cc6a847cd921f06d2f1fb0d012025-08-20T02:17:53ZengNature Publishing GroupCell Death Discovery2058-77162025-04-0111111310.1038/s41420-025-02474-0Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogasterRuchi Umargamwala0Shannon Nicolson1Jantina Manning2Julian M. Carosi3Sharad Kumar4Donna Denton5Centre for Cancer Biology, University of South AustraliaCentre for Cancer Biology, University of South AustraliaCentre for Cancer Biology, University of South AustraliaSouth Australian Health and Medical Research InstituteCentre for Cancer Biology, University of South AustraliaCentre for Cancer Biology, University of South AustraliaAbstract 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.https://doi.org/10.1038/s41420-025-02474-0 |
| spellingShingle | Ruchi Umargamwala Shannon Nicolson Jantina Manning Julian M. Carosi Sharad Kumar Donna Denton Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogaster Cell Death Discovery |
| title | Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogaster |
| title_full | Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogaster |
| title_fullStr | Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogaster |
| title_full_unstemmed | Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogaster |
| title_short | Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogaster |
| title_sort | identification of new candidates regulating autophagy dependent midgut degradation in drosophila melanogaster |
| url | https://doi.org/10.1038/s41420-025-02474-0 |
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