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Functional Characterisation of the Autophagy ATG12~5/16 Complex in Dictyostelium discoideum

Karow, Malte and Fischer, Sarah and Meßling, Susanne and Konertz, Roman and Riehl, Jana and Xiong, Qiuhong and Rijal, Ramesh and Wagle, Prerana and Clemen, Christoph S. and Eichinger, Ludwig (2020) Functional Characterisation of the Autophagy ATG12~5/16 Complex in Dictyostelium discoideum. Cells, 9 (5), p. 1179. Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/cells9051179. ISSN 2073-4409.

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Official URL: https://www.mdpi.com/2073-4409/9/5/1179/htm

Abstract

Macroautophagy, a highly conserved and complex intracellular degradative pathway, involves more than 20 core autophagy (ATG) proteins, among them the hexameric ATG12~5/16 complex, which is part of the essential ubiquitin-like conjugation systems in autophagy. Dictyostelium discoideum atg5 single, atg5/12 double, and atg5/12/16 triple gene knock-out mutant strains displayed similar defects in the conjugation of ATG8 to phosphatidylethanolamine, development, and cell viability upon nitrogen starvation. This implies that ATG5, 12 and 16 act as a functional unit in canonical autophagy. Macropinocytosis of TRITC dextran and phagocytosis of yeast were significantly decreased in ATG5¯ and ATG5¯/12¯ and even further in ATG5¯/12¯/16¯ cells. In contrast, plaque growth on Klebsiella aerogenes was about twice as fast for ATG5¯ and ATG5¯/12¯/16¯ cells in comparison to AX2, but strongly decreased for ATG5¯/12¯ cells. Along this line, phagocytic uptake of Escherichia coli was significantly reduced in ATG5¯/12¯ cells, while no difference in uptake, but a strong increase in membrane association of E. coli, was seen for ATG5¯ and ATG5¯/12¯/16¯ cells. Proteasomal activity was also disturbed in a complex fashion, consistent with an inhibitory activity of ATG16 in the absence of ATG5 and/or ATG12. Our results confirm the essential function of the ATG12~5/16 complex in canonical autophagy, and furthermore are consistent with autophagy-independent functions of the complex and its individual components. They also strongly support the placement of autophagy upstream of the ubiquitin-proteasome system (UPS), as a fully functional UPS depends on autophagy.

Item URL in elib:https://elib.dlr.de/135894/
Document Type:Article
Title:Functional Characterisation of the Autophagy ATG12~5/16 Complex in Dictyostelium discoideum
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Karow, MalteCentre for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, GermanyUNSPECIFIED
Fischer, SarahCentre for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, GermanyUNSPECIFIED
Meßling, SusanneCentre for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, GermanyUNSPECIFIED
Konertz, RomanCentre for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germanyhttps://orcid.org/0000-0002-6488-1885
Riehl, JanaCentre for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, GermanyUNSPECIFIED
Xiong, QiuhongInstitute of Biomedical Sciences, Shanxi University, No. 92 Wucheng Road, Taiyuan 030006, ChinaUNSPECIFIED
Rijal, RameshDepartment of Biology, Texas A&M University, College Station, TX 77843-3474, USAhttps://orcid.org/0000-0003-0498-1064
Wagle, PreranaBioinformatics Core Facility, CECAD Research Center, University of Cologne, 50931 Cologne, GermanyUNSPECIFIED
Clemen, Christoph S.Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, GermanyUNSPECIFIED
Eichinger, LudwigCentre for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germanyhttps://orcid.org/0000-0003-1594-6117
Date:9 May 2020
Journal or Publication Title:Cells
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:9
DOI :10.3390/cells9051179
Page Range:p. 1179
Publisher:Multidisciplinary Digital Publishing Institute (MDPI)
ISSN:2073-4409
Status:Published
Keywords:ATG12~5/16 complex; autophagy; Dictyostelium; ubiquitin-like protein; phagocytosis; pinocytosis; proteasome; UPS
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Vorhaben Systemphysiologie (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Muscle and Bone Metabolism
Deposited By: Arndt, Carina
Deposited On:03 Sep 2020 15:14
Last Modified:31 Oct 2020 04:35

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