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ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans

Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, Germany
International Max Planck Research School ‘From Molecules to Organisms’, Max Planck Institute for Developmental Biology and Eberhard Karls University, 72076 Tuebingen, Germany
Author to whom correspondence should be addressed.
Cells 2019, 8(3), 236;
Received: 31 January 2019 / Revised: 25 February 2019 / Accepted: 6 March 2019 / Published: 12 March 2019
(This article belongs to the Special Issue Proteostasis and Autophagy)
PDF [4099 KB, uploaded 27 March 2019]


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. View Full-Text
Keywords: ATG-18; autophagy; EPG-6; GFP::LGG-1; lifespan; WIPI3; WIPI4 ATG-18; autophagy; EPG-6; GFP::LGG-1; lifespan; WIPI3; WIPI4

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Takacs, Z.; Sporbeck, K.; Stoeckle, J.; Prado Carvajal, M.J.; Grimmel, M.; Proikas-Cezanne, T. ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans. Cells 2019, 8, 236.

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