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


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.

SUBMITTER: Karow M 

PROVIDER: S-EPMC7290328 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Functional Characterisation of the Autophagy ATG12~5/16 Complex in <i>Dictyostelium discoideum</i>.

Karow Malte M   Fischer Sarah S   Meßling Susanne S   Konertz Roman R   Riehl Jana J   Xiong Qiuhong Q   Rijal Ramesh R   Wagle Prerana P   Clemen Christoph S CS   Eichinger Ludwig L  

Cells 20200509 5


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. <i>Dictyostelium discoideum</i><i>atg5</i> single, <i>atg5</i><i>/</i><i>12</i> double, and <i>atg5</i><i>/</i><i>12</i><i>/</i><i>16</i> triple gene knock-out mutant strains displayed similar defects in the conjugation of ATG8 to phosphati  ...[more]

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