ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans
During macroautophagy, the human WIPI (WD-repeat protein interacting with phosphoinositides) proteins (WIPI1–4) function as phosphatidylinositol 3-phosphate effectors at the nascent autophagosome. Likewise, the two WIPI homologues in Caenorhabditis elegans, ATG-18 and EPG-6, play important...
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| Format: | Article |
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MDPI AG
2019-03-01
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| Online Access: | http://www.mdpi.com/2073-4409/8/3/236 |
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| author | Zsuzsanna Takacs Katharina Sporbeck Jennifer Stoeckle Maria Jhaneth Prado Carvajal Mona Grimmel Tassula Proikas-Cezanne |
| author_facet | Zsuzsanna Takacs Katharina Sporbeck Jennifer Stoeckle Maria Jhaneth Prado Carvajal Mona Grimmel Tassula Proikas-Cezanne |
| author_sort | Zsuzsanna Takacs |
| collection | DOAJ |
| description | During macroautophagy, the human WIPI (WD-repeat protein interacting with phosphoinositides) proteins (WIPI1–4) function as phosphatidylinositol 3-phosphate effectors at the nascent autophagosome. Likewise, the two WIPI homologues in Caenorhabditis elegans, ATG-18 and EPG-6, play important roles in autophagy, whereby ATG-18 is considered to act upstream of EPG-6 at the onset of autophagy. Due to its essential role in autophagy, ATG-18 was found to be also essential for lifespan extension in Caenorhabditis elegans; however, this has not yet been addressed with regard to EPG-6. Here, we wished to address this point and generated mutant strains that expressed the autophagy marker GFP::LGG-1 (GFP-LC3 in mammals) and harbored functional deletions of either atg-18 (atg18(gk378)), epg-6 (epg-6(bp242)) or both (atg-18(gk378);epg-6(bp242)). Using quantitative fluorescence microscopy, Western blotting, and lifespan assessments, we provide evidence that in the absence of either ATG-18 or EPG-6 autophagy was impaired, and while atg-18 mutant animals showed a short-lived phenotype, lifespan was significantly increased in epg-6 mutant animals. We speculate that the long-lived phenotype of epg-6 mutant animals points towards an autophagy-independent function of EPG-6 in lifespan control that warrants further mechanistic investigations in future studies. |
| first_indexed | 2024-03-12T06:20:54Z |
| format | Article |
| id | doaj.art-7ca9e66982ba4524b5ac2003a4085c45 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:20:54Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7ca9e66982ba4524b5ac2003a4085c452023-09-03T02:15:48ZengMDPI AGCells2073-44092019-03-018323610.3390/cells8030236cells8030236ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegansZsuzsanna Takacs0Katharina Sporbeck1Jennifer Stoeckle2Maria Jhaneth Prado Carvajal3Mona Grimmel4Tassula Proikas-Cezanne5Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, GermanyDepartment of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, GermanyDuring macroautophagy, the human WIPI (WD-repeat protein interacting with phosphoinositides) proteins (WIPI1–4) function as phosphatidylinositol 3-phosphate effectors at the nascent autophagosome. Likewise, the two WIPI homologues in Caenorhabditis elegans, ATG-18 and EPG-6, play important roles in autophagy, whereby ATG-18 is considered to act upstream of EPG-6 at the onset of autophagy. Due to its essential role in autophagy, ATG-18 was found to be also essential for lifespan extension in Caenorhabditis elegans; however, this has not yet been addressed with regard to EPG-6. Here, we wished to address this point and generated mutant strains that expressed the autophagy marker GFP::LGG-1 (GFP-LC3 in mammals) and harbored functional deletions of either atg-18 (atg18(gk378)), epg-6 (epg-6(bp242)) or both (atg-18(gk378);epg-6(bp242)). Using quantitative fluorescence microscopy, Western blotting, and lifespan assessments, we provide evidence that in the absence of either ATG-18 or EPG-6 autophagy was impaired, and while atg-18 mutant animals showed a short-lived phenotype, lifespan was significantly increased in epg-6 mutant animals. We speculate that the long-lived phenotype of epg-6 mutant animals points towards an autophagy-independent function of EPG-6 in lifespan control that warrants further mechanistic investigations in future studies.http://www.mdpi.com/2073-4409/8/3/236ATG-18autophagyEPG-6GFP::LGG-1lifespanWIPI3WIPI4 |
| spellingShingle | Zsuzsanna Takacs Katharina Sporbeck Jennifer Stoeckle Maria Jhaneth Prado Carvajal Mona Grimmel Tassula Proikas-Cezanne ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans Cells ATG-18 autophagy EPG-6 GFP::LGG-1 lifespan WIPI3 WIPI4 |
| title | ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans |
| title_full | ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans |
| title_fullStr | ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans |
| title_full_unstemmed | ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans |
| title_short | ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans |
| title_sort | atg 18 and epg 6 are both required for autophagy but differentially contribute to lifespan control in caenorhabditis elegans |
| topic | ATG-18 autophagy EPG-6 GFP::LGG-1 lifespan WIPI3 WIPI4 |
| url | http://www.mdpi.com/2073-4409/8/3/236 |
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