Linking Lysosomal Trafficking Defects with Changes in Aging and Stress Response in Drosophila
Open accessAbstract
Defects in pathways that direct cellular components to the lysosome for degradation are often linked with a decrease in viability and with progressive disorders. Previously we had shown that blue cheese (bchs: Drosophila homologue of human Alfy) mutations lead to reduced longevity and the accumulation of ubiquitinated neural aggregates. A genetic modifier screen based on overexpression of Bchs in the eye was used to identify several potential genetic interactions, which included autophagic and endocytic trafficking genes as well as cytoskeletal and motor proteins and members of the SUMO and ubiquitin signaling pathways. We found that mutations in several of the genes identified in the screen also result in bchs-like phenotypes, including a reduction in adult lifespan and changes in ubiquitinated protein profiles. In addition, we show that Bchs modifiers belonging to the autophagic and trans-Golgi trafficking pathways also display defects in adult starvation response. Our data further support a role for Bchs/Alfy in the autophagic pathway and strongly indicate that autophagy plays an important role in aging and stress response.Addendum to:Genetic Modifiers of the Drosophila Blue Cheese Gene Link Defects in Lysosomal Transport with Decreased Lifespan and Altered Ubiquitinated Protein ProfilesA. Simonsen, R. Cumming, K. Lindmo, V. Galaviz, S. Cheng, T. Rusten and K. FinleyGenetics 2007; In press
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In flies, expression of specific autophagy genes prolongs lifespan and provides resistance to particular stressors.
“recent work in flies has shown that expression of specific autophagy genes prolongs lifespan and provides resistance to particular stressors (Simonsen et al., 2007)”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Simonsen et al., 2007
The paper reports in its Abstract that mutations in several autophagy-related genes reduce adult fly lifespan, and its starvation-response section reports increased starvation sensitivity in atg8a mutants. These findings link the genes to longevity and stress response, but the paper does not show that expressing those genes prolongs lifespan or increases stress resistance. Its Bchs overexpression experiment concerns an eye phenotype, not either claimed benefit. (LLM, conf=0.83)
Experimental — accuracy not yet measuredStudies 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 Simonsen et al., 2007
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Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Autophagy as a regulated pathway of cellular degradation.
Klionsky, D., & Emr, S. (2000) · Science · doi:10.1126/science.290.5497.1717 · Cited by 3,794 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
Bjørkøy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Øvervatn, A., Stenmark, H., & Johansen, T. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200507002 · Cited by 3,276 · see citing works
The role of autophagy during the early neonatal starvation period
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865 · see citing works
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study
Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A., & Cuervo, A. M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.113 · Cited by 1,588 · see citing works
A Unified Nomenclature for Yeast Autophagy-Related Genes
Klionsky, D. J., Cregg, J. M., Dunn, W. A., Emr, S. D., Sakai, Y., Sandoval, I. V., Sibirny, A. А., Subramani, S. E., Thumm, M., Marten Veenhuis, A., et al. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00296-x · Cited by 1,267 · see citing works
Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy
Ravikumar, B. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.9.1107 · Cited by 1,099 · see citing works
Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body
Scott, R. C., Schuldiner, O., & Neufeld, T. P. (2004) · Developmental Cell · doi:10.1016/j.devcel.2004.07.009 · Cited by 963 · see citing works
Human IRGM Induces Autophagy to Eliminate Intracellular Mycobacteria
Singh, S. B., Davis, A. S., Taylor, G. A., & Deretic, V. (2006) · Science · doi:10.1126/science.1129577 · Cited by 915 · see citing works
Adaptable adaptors for coated vesicles.
Robinson, M. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2004.02.002 · Cited by 741 · see citing works
Dell’Angelica, E. C., Mullins, C., Caplan, S., & Bonifacino, J. S. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.10.1265 · Cited by 503 · see citing works
Protein sorting into multivesicular endosomes
Raiborg, C., Rusten, T. E., & Stenmark, H. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00080-2 · Cited by 500 · see citing works
Rusten, T. E., Lindmo, K., Juhász, G., Sass, M., Seglen, P. O., Brech, A., & Stenmark, H. (2004) · Developmental Cell · doi:10.1016/j.devcel.2004.07.005 · Cited by 487 · see citing works
Dynein mutations impair autophagic clearance of aggregate-prone proteins
Ravikumar, B., Acevedo‐Arozena, A., Imarisio, S., Berger, Z., Vacher, C., O’Kane, C. J., Brown, S. D. M., & Rubinsztein, D. C. (2005) · Nature Genetics · doi:10.1038/ng1591 · Cited by 458 · see citing works
Gunawardena, S., & Goldstein, L. S. B. (2001) · Neuron · doi:10.1016/s0896-6273(01)00496-2 · Cited by 428 · see citing works
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Shih, S. C., Katzmann, D. J., Schnell, J. D., Sutanto, M. A., Emr, S. D., & Hicke, L. (2002) · Nature Cell Biology · doi:10.1038/ncb790 · Cited by 418 · see citing works
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Nixon, R. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.07.003 · Cited by 337 · see citing works
Simonsen, A., Birkeland, H. C. G., Gillooly, D. J., Mizushima, N., Kuma, A., Yoshimori, T., Slagsvold, T., Brech, A., & Stenmark, H. (2004) · Journal of Cell Science · doi:10.1242/jcs.01287 · Cited by 282 · see citing works
Self-citationA SAGE Approach to Discovery of Genes Involved in Autophagic Cell Death
Gorski, S. M., Chittaranjan, S., Pleasance, E. D., Freeman, J. D., Anderson, C. L., Varhol, R. J., Coughlin, S. M., Zuyderduyn, S. D., Jones, S. J. M., & Marra, M. A. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00082-4 · Cited by 213 · see citing works
Torroja, L., Chu, H., Kotovsky, I., & White, K. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80215-2 · Cited by 203 · see citing works
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Kraut, R. S., Menon, K. P., & Zinn, K. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00124-5 · Cited by 183 · see citing works
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Carvalho, G. B., Kapahi, P., & Benzer, S. (2005) · Nature Methods · doi:10.1038/nmeth798 · Cited by 164 · see citing works
blue cheeseMutations Define a Novel, Conserved Gene Involved in Progressive Neural Degeneration
Finley, K. D., Edeen, P. T., Cumming, R. C., Mardahl‐Dumesnil, M., Taylor, B. J., Rodriguez, M. H., Hwang, C. E., Benedetti, M., & McKeown, M. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01254.2003 · Cited by 113 · see citing works
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Self-citationSimonsen, A., Cumming, R. C., Lindmo, K., Galaviz, V., Cheng, S., Rusten, T. E., & Finley, K. D. (2007) · Genetics · doi:10.1534/genetics.106.065011 · Cited by 67 · see citing works
Self-citationMembrane traffic to and from lysosomes.
Luzio, J. P., Pryor, P. R., Gray, S. R., Gratian, M. J., Piper, R. C., & Bright, N. A. (2005) · Biochemical Society Symposia · doi:10.1042/bss0720077 · Cited by 61 · see citing works
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Self-citation
- Authors
- Simonsen, A., Cumming, R. C., & Finley, K. D.
- Affiliations
- Salk Institute for Biological Studies (US)
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2007-09-20
- Volume
- 3
- Issue
- 5
- Pages
- 499-501
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W2048853932
- Cited by
- 37
- References
- 27
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2016: 1 · 2014: 4 · 2013: 1 · 2012: 4
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Norges Forskningsråd
- National Institutes of Health
- 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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- lysosomal trafficking, aging, lifespan, genetic modifiers, ubiquitinated protein aggregates, starvation response, stress response, endosomal trafficking, ubiquitin signaling, Drosophila
- MeSH terms
- Aging, Animals, Autophagy, Drosophila, Humans, Lysosomes, Mutation, Nerve Tissue Proteins, Signal Transduction, Genes, Insect, Drosophila Proteins
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