Larval midgut destruction in Drosophila: Not dependent on caspases but suppressed by the loss of autophagy
Open accessAbstract
While most programmed cell death (PCD) in animal development is reliant upon the caspase-dependent apoptotic pathway and subsequent cleavage of caspase substrates, we found that PCD in Drosophila larval midgut occurs normally in the absence of the main components of the apoptotic machinery. However, when some of the components of the autophagic machinery were disrupted, midgut destruction was severely delayed. These studies demonstrate that Drosophila midgut PCD is executed by a novel mechanism where caspases are apparently dispensable, but that requires autophagy.
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Autophagy is critical for Drosophila midgut cell death, which is accompanied by transcriptional upregulation of all of the Atg genes tested, including Atg8a.
“Autophagy is critical for Drosophila midgut cell death, which is accompanied by transcriptional upregulation of all of the Atg genes tested, including Atg8a (Fig. 18).199,451”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [451]
The Abstract says that disrupting autophagy severely delays Drosophila larval midgut destruction and that several Atg genes are transcriptionally upregulated during midgut cell death. It does not say that all Atg genes tested were upregulated or identify Atg8a as one of them; it describes Atg8a as a marker of autophagic puncta. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn developing D. melanogaster midgut, caspase inactivation has no consequences, whereas mutations or deletions in essential Atg genes suppress midgut tissue degradation.
“Thus, whereas the genetic inactivation of caspases in the midgut of developing D. melanogaster has no consequences, mutations or deletions in essential autophagy-related (Atg) genes suppress midgut tissue degradation [827–829].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [827]
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Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
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Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy
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Self-citationKlionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationEssential versus accessory aspects of cell death: recommendations of the NCCD 2015
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Self-citationRelationship between growth arrest and autophagy in midgut programmed cell death in Drosophila
Denton, D., Chang, T.-K., Nicolson, S., Shravage, B., Simin, R., Baehrecke, E. H., & Kumar, S. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.43 · Cited by 81 · see citing works
Self-citationDistinct requirements of Autophagy-related genes in programmed cell death
Xu, T., Nicolson, S., Denton, D., & Kumar, S. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2015.28 · Cited by 75 · see citing works
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- Authors
- Denton, D., Shravage, B. V., Simin, R., Baehrecke, E. H., & Kumar, S.
- Affiliations
- South Australia Pathology (AU)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Kumar, Sharad
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2010-01
- Volume
- 6
- Issue
- 1
- Pages
- 163-165
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC2819273
- OpenAlex
- W2015522350
- Cited by
- 54
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 8
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM079431)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- programmed cell death, caspase-independent cell death, apoptosis, developmental cell death
- MeSH terms
- Animals, Autophagy, Drosophila, Intestinal Mucosa, Intestines, Larva, Models, Biological, Cell Death, Body Patterning, Caspases
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