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

1
Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, Germany
2
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; https://doi.org/10.3390/cells8030236
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)
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Abstract

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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