Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila
Open accessAbstract
Autophagy, a cellular process of cytoplasmic degradation and recycling, is induced in Drosophila larval tissues during metamorphosis, potentially contributing to their destruction or reorganization. Unexpectedly, we find that flies lacking the core autophagy regulator Atg7 are viable, despite severe defects in autophagy. Although metamorphic cell death is perturbed in Atg7 mutants, the larval–adult midgut transition proceeds normally, with extended pupal development compensating for reduced autophagy. Atg7−/− adults are short-lived, hypersensitive to nutrient and oxidative stress, and accumulate ubiquitin-positive aggregates in degenerating neurons. Thus, normal levels of autophagy are crucial for stress survival and continuous cellular renewal, but not metamorphosis.
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Studies in worms and flies support that functional macroautophagy is necessary to preserve normal lifespan.
“studies by other groups in worms and flies seem to support that functional macroautophagy is necessary to preserve normal lifespan (Juhasz et al., 2007; Morck and Pilon, 2006; Simonsen et al., 2007)”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Juhasz et al., 2007
In flies, increasing autophagy in neurons alone is sufficient to extend lifespan, and reducing autophagy shortens lifespan and gives rise to neurodegeneration.
“In flies, increasing autophagy in neurons alone is sufficient to extend lifespan (52), and reducing autophagy shortens lifespan and gives rise to neurodegeneration (52,53).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [53]
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- Authors
- Juhász, G., Érdi, B., Sass, M., & Neufeld, T. P.
- Affiliations
- Eötvös Loránd University (HU)
- University of Minnesota (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2007-12-01
- Volume
- 21
- Issue
- 23
- Pages
- 3061-3066
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2081972
- OpenAlex
- W2165081183
- Cited by
- 396
- References
- 18
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 16 · 2023: 11 · 2022: 20 · 2021: 27 · 2020: 24 · 2019: 36 · 2018: 24 · 2017: 16 · 2016: 30 · 2015: 22 · 2014: 22 · 2013: 22 · 2012: 23
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- ELTE Digital Institutional Repository (EDIT) (Eötvös Loránd University) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01 GM62509, R01GM062509)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- autophagy, ATG7, Drosophila metamorphosis, neuronal health, stress tolerance, longevity, oxidative stress, nutritional stress, neurodegeneration, pupal development, cell regeneration
- MeSH terms
- Autophagy-Related Protein 7, Animals, Autophagy, Digestive System, Drosophila, Larva, Longevity, Male, Metamorphosis, Biological, Mutation, Nerve Degeneration, Neurons, Starvation, Genes, Insect, Gene Deletion, Oxidative Stress, Drosophila Proteins, Ubiquitin-Activating Enzymes
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