Autophagy, Not Apoptosis, Is Essential for Midgut Cell Death in Drosophila
Open accessAbstract
Most developmentally programmed cell death in metazoans is mediated by caspases. During Drosophila metamorphosis, obsolete tissues, including the midgut and salivary glands, are removed by programmed cell death [1]. The initiator caspase Dronc and its activator Ark are required for the death of salivary glands, but not for midgut removal [2, 3]. In addition to caspases, complete removal of salivary glands requires autophagy [4]. However, the contribution of autophagy to midgut cell death has not been explored. Examination of combined mutants of the main initiator and effector caspases revealed that the canonical apoptotic pathway is not required for midgut cell death. Further analyses revealed that the caspase Decay is responsible for most of the caspase activity in dying midguts, yet inhibition of this activity has no effect on midgut removal. By contrast, midgut degradation was severely delayed by inhibition of autophagy, and this occurred without a decrease in caspase activity. Surprisingly, the combined inhibition of caspases and autophagy did not result in an additional delay in midgut removal. Together, our results indicate that autophagy, not caspases, is essential for midgut programmed cell death, providing the first in vivo evidence of caspase-independent programmed cell death that requires autophagy despite the presence of high caspase activity.
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In 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 [828]
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- Authors
- Denton, D., Shravage, B., Simin, R., Mills, K., Berry, D. L., Baehrecke, E. H., & Kumar, S.
- Affiliations
- Centre for Cancer Biology (AU)
- University of Massachusetts Chan Medical School (US)
- South Australia Pathology (AU)
- Georgetown University (US)
- Corresponding author
- Kumar, Sharad
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 19
- Issue
- 20
- Pages
- 1741-1746
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC2783269
- OpenAlex
- W2067684692
- Cited by
- 385
- References
- 33
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 16 · 2023: 17 · 2022: 14 · 2021: 23 · 2020: 28 · 2019: 21 · 2018: 24 · 2017: 22 · 2016: 25 · 2015: 33 · 2014: 30 · 2013: 27 · 2012: 31
- FWCI
- 16.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- National Institute of General Medical Sciences (R01GM059136, R01GM079431)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- autophagy, programmed cell death, Drosophila metamorphosis, caspase-independent cell death, salivary gland removal, tissue degradation
- MeSH terms
- Animals, Autophagy, Drosophila, Metamorphosis, Biological, Apoptosis, Body Patterning, Caspases, Drosophila Proteins
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