Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body
In response to starvation, eukaryotic cells recover nutrients through autophagy, a lysosomal-mediated process of cytoplasmic degradation. Autophagy is known to be inhibited by TOR signaling, but the mechanisms of autophagy regulation and its role in TOR-mediated cell growth are unclear. Here, we sho...
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| Veröffentlicht in: | Developmental cell 2004-08, Vol.7 (2), p.167-178 |
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| creator | Scott, Ryan C. Schuldiner, Oren Neufeld, Thomas P. |
| description | In response to starvation, eukaryotic cells recover nutrients through autophagy, a lysosomal-mediated process of cytoplasmic degradation. Autophagy is known to be inhibited by TOR signaling, but the mechanisms of autophagy regulation and its role in TOR-mediated cell growth are unclear. Here, we show that signaling through TOR and its upstream regulators PI3K and Rheb is necessary and sufficient to suppress starvation-induced autophagy in the
Drosophila fat body. In contrast, TOR's downstream effector S6K promotes rather than suppresses autophagy, suggesting S6K downregulation may limit autophagy during extended starvation. Despite the catabolic potential of autophagy, disruption of conserved components of the autophagic machinery, including
ATG1 and
ATG5, does not restore growth to
TOR mutant cells. Instead, inhibition of autophagy enhances
TOR mutant phenotypes, including reduced cell size, growth rate, and survival. Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor. |
| doi_str_mv | 10.1016/j.devcel.2004.07.009 |
| format | Article |
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Drosophila fat body. In contrast, TOR's downstream effector S6K promotes rather than suppresses autophagy, suggesting S6K downregulation may limit autophagy during extended starvation. Despite the catabolic potential of autophagy, disruption of conserved components of the autophagic machinery, including
ATG1 and
ATG5, does not restore growth to
TOR mutant cells. Instead, inhibition of autophagy enhances
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Drosophila fat body. In contrast, TOR's downstream effector S6K promotes rather than suppresses autophagy, suggesting S6K downregulation may limit autophagy during extended starvation. Despite the catabolic potential of autophagy, disruption of conserved components of the autophagic machinery, including
ATG1 and
ATG5, does not restore growth to
TOR mutant cells. Instead, inhibition of autophagy enhances
TOR mutant phenotypes, including reduced cell size, growth rate, and survival. Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor.</description><subject>Animals</subject><subject>Autophagy</subject><subject>Autophagy-Related Proteins</subject><subject>Cell Division</subject><subject>Cell Survival</subject><subject>Cytoplasm - metabolism</subject><subject>Drosophila</subject><subject>Drosophila - physiology</subject><subject>Drosophila melanogaster</subject><subject>Drosophila Proteins - physiology</subject><subject>Fat Body - physiology</subject><subject>Food Deprivation</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Lysosomes - metabolism</subject><subject>Microscopy, Electron</subject><subject>Models, Biological</subject><subject>Phagocytosis</subject><subject>Phenotype</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - physiology</subject><subject>Protein Kinases - physiology</subject><subject>Ribosomal Protein S6 Kinases - metabolism</subject><subject>Saccharomyces cerevisiae Proteins - physiology</subject><subject>Signal Transduction</subject><subject>Time Factors</subject><subject>TOR Serine-Threonine Kinases</subject><issn>1534-5807</issn><issn>1878-1551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMlOwzAURS0EYv4DhLxil_A8xekGCcooVSAxrC0Tv4CrNC5xUql_j0srsYOVB517n94h5IRBzoAV59Pc4aLCJucAMgedA4y2yD4rdZkxpdh2uishM1WC3iMHMU4hxVgJu2SPKT4qNJP75PE5NEht6-gzfgyN7X1oaajpS2-7xc8re2jdUKGjl0Mf5p_2Y0l9S_tPpNddiOnHN5be2p5eBbc8Iju1bSIeb85D8nZ78zq-zyZPdw_jy0lWKWB9JriqpEI3khUqFFLUUEuHCBY4t8CEFooLyRxzWinEwikQ705xXo507UpxSM7WvfMufA0YezPzMclobIthiKYotAZeFP-CyYcCLkQC5Rqs0laxw9rMOz-z3dIwMCvhZmrWws1KuAFtkvAUO930D-8zdL-hjeEEXKwBTDoWHjsTK49tEuo7rHrjgv97wjdb9JIe</recordid><startdate>20040801</startdate><enddate>20040801</enddate><creator>Scott, Ryan C.</creator><creator>Schuldiner, Oren</creator><creator>Neufeld, Thomas P.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20040801</creationdate><title>Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body</title><author>Scott, Ryan C. ; Schuldiner, Oren ; Neufeld, Thomas P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-325c45ed94ce5e343f0f4dee0a022a0137352341d1d755ee6d503bd522897fd83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Autophagy</topic><topic>Autophagy-Related Proteins</topic><topic>Cell Division</topic><topic>Cell Survival</topic><topic>Cytoplasm - metabolism</topic><topic>Drosophila</topic><topic>Drosophila - physiology</topic><topic>Drosophila melanogaster</topic><topic>Drosophila Proteins - physiology</topic><topic>Fat Body - physiology</topic><topic>Food Deprivation</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Lysosomes - metabolism</topic><topic>Microscopy, Electron</topic><topic>Models, Biological</topic><topic>Phagocytosis</topic><topic>Phenotype</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - physiology</topic><topic>Protein Kinases - physiology</topic><topic>Ribosomal Protein S6 Kinases - metabolism</topic><topic>Saccharomyces cerevisiae Proteins - physiology</topic><topic>Signal Transduction</topic><topic>Time Factors</topic><topic>TOR Serine-Threonine Kinases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scott, Ryan C.</creatorcontrib><creatorcontrib>Schuldiner, Oren</creatorcontrib><creatorcontrib>Neufeld, Thomas P.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Developmental cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scott, Ryan C.</au><au>Schuldiner, Oren</au><au>Neufeld, Thomas P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body</atitle><jtitle>Developmental cell</jtitle><addtitle>Dev Cell</addtitle><date>2004-08-01</date><risdate>2004</risdate><volume>7</volume><issue>2</issue><spage>167</spage><epage>178</epage><pages>167-178</pages><issn>1534-5807</issn><eissn>1878-1551</eissn><abstract>In response to starvation, eukaryotic cells recover nutrients through autophagy, a lysosomal-mediated process of cytoplasmic degradation. Autophagy is known to be inhibited by TOR signaling, but the mechanisms of autophagy regulation and its role in TOR-mediated cell growth are unclear. Here, we show that signaling through TOR and its upstream regulators PI3K and Rheb is necessary and sufficient to suppress starvation-induced autophagy in the
Drosophila fat body. In contrast, TOR's downstream effector S6K promotes rather than suppresses autophagy, suggesting S6K downregulation may limit autophagy during extended starvation. Despite the catabolic potential of autophagy, disruption of conserved components of the autophagic machinery, including
ATG1 and
ATG5, does not restore growth to
TOR mutant cells. Instead, inhibition of autophagy enhances
TOR mutant phenotypes, including reduced cell size, growth rate, and survival. Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15296714</pmid><doi>10.1016/j.devcel.2004.07.009</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Autophagy Autophagy-Related Proteins Cell Division Cell Survival Cytoplasm - metabolism Drosophila Drosophila - physiology Drosophila melanogaster Drosophila Proteins - physiology Fat Body - physiology Food Deprivation Gene Expression Regulation, Developmental Lysosomes - metabolism Microscopy, Electron Models, Biological Phagocytosis Phenotype Phosphatidylinositol 3-Kinases - metabolism Phosphatidylinositol 3-Kinases - physiology Protein Kinases - physiology Ribosomal Protein S6 Kinases - metabolism Saccharomyces cerevisiae Proteins - physiology Signal Transduction Time Factors TOR Serine-Threonine Kinases |
| title | Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body |
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