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Cells. 2019 Mar 12;8(3). pii: E236. doi: 10.3390/cells8030236.

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

Author information

1
Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, Germany. zsuzsanna.takacs@imba.oeaw.ac.at.
2
International Max Planck Research School 'From Molecules to Organisms', Max Planck Institute for Developmental Biology and Eberhard Karls University, 72076 Tuebingen, Germany. zsuzsanna.takacs@imba.oeaw.ac.at.
3
Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, Germany. katharina.sporbeck@student.uni-tuebingen.de.
4
International Max Planck Research School 'From Molecules to Organisms', Max Planck Institute for Developmental Biology and Eberhard Karls University, 72076 Tuebingen, Germany. katharina.sporbeck@student.uni-tuebingen.de.
5
Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, Germany. jennifer.stoeckle@uni-hohenheim.de.
6
Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, Germany. maria-jhaneth.prado-carvajal@student.uni-tuebingen.de.
7
Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, Germany. mona.grimmel@med.uni-tuebingen.de.
8
Department of Molecular Biology, Interfaculty Institute of Cell Biology, Eberhard Karls University, 72076 Tuebingen, Germany. tassula.proikas-cezanne@uni-tuebingen.de.
9
International Max Planck Research School 'From Molecules to Organisms', Max Planck Institute for Developmental Biology and Eberhard Karls University, 72076 Tuebingen, Germany. tassula.proikas-cezanne@uni-tuebingen.de.

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.

KEYWORDS:

ATG-18; EPG-6; GFP::LGG-1; WIPI3; WIPI4; autophagy; lifespan

PMID:
30871075
PMCID:
PMC6468378
DOI:
10.3390/cells8030236
[Indexed for MEDLINE]
Free PMC Article

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