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Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans

Autophagy is a mechanism responsible for intracellular degradation and recycling of macromolecules and organelles, essential for cell survival in adverse conditions. More than 40 autophagy-related (ATG) genes have been identified and characterized in fungi, among them ATG4 and ATG8. ATG4 encodes a c...

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Autores principales: Roberto, Thiago Nunes, Lima, Ricardo Ferreira, Pascon, Renata Castiglioni, Idnurm, Alexander, Vallim, Marcelo Afonso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135279/
https://www.ncbi.nlm.nih.gov/pubmed/32251488
http://dx.doi.org/10.1371/journal.pone.0230981
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author Roberto, Thiago Nunes
Lima, Ricardo Ferreira
Pascon, Renata Castiglioni
Idnurm, Alexander
Vallim, Marcelo Afonso
author_facet Roberto, Thiago Nunes
Lima, Ricardo Ferreira
Pascon, Renata Castiglioni
Idnurm, Alexander
Vallim, Marcelo Afonso
author_sort Roberto, Thiago Nunes
collection PubMed
description Autophagy is a mechanism responsible for intracellular degradation and recycling of macromolecules and organelles, essential for cell survival in adverse conditions. More than 40 autophagy-related (ATG) genes have been identified and characterized in fungi, among them ATG4 and ATG8. ATG4 encodes a cysteine protease (Atg4) that plays an important role in autophagy by initially processing Atg8 at its C-terminus region. Atg8 is a ubiquitin-like protein essential for the synthesis of the double-layer membrane that constitutes the autophagosome vesicle, responsible for delivering the cargo from the cytoplasm to the vacuole lumen. The contributions of Atg-related proteins in the pathogenic yeast in the genus Cryptococcus remain to be explored, to elucidate the molecular basis of the autophagy pathway. In this context, we aimed to investigate the role of autophagy-related proteins 4 and 8 (Atg4 and Atg8) during autophagy induction and their contribution with non-autophagic events in C. neoformans. We found that Atg4 and Atg8 are conserved proteins and that they interact physically with each other. ATG gene deletions resulted in cells sensitive to nitrogen starvation. ATG4 gene disruption affects Atg8 degradation and its translocation to the vacuole lumen, after autophagy induction. Both atg4 and atg8 mutants are more resistant to oxidative stress, have an impaired growth in the presence of the cell wall-perturbing agent Congo Red, and are sensitive to the proteasome inhibitor bortezomib (BTZ). By that, we conclude that in C. neoformans the autophagy-related proteins Atg4 and Atg8 play an important role in the autophagy pathway; which are required for autophagy regulation, maintenance of amino acid levels and cell adaptation to stressful conditions.
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spelling pubmed-71352792020-04-09 Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans Roberto, Thiago Nunes Lima, Ricardo Ferreira Pascon, Renata Castiglioni Idnurm, Alexander Vallim, Marcelo Afonso PLoS One Research Article Autophagy is a mechanism responsible for intracellular degradation and recycling of macromolecules and organelles, essential for cell survival in adverse conditions. More than 40 autophagy-related (ATG) genes have been identified and characterized in fungi, among them ATG4 and ATG8. ATG4 encodes a cysteine protease (Atg4) that plays an important role in autophagy by initially processing Atg8 at its C-terminus region. Atg8 is a ubiquitin-like protein essential for the synthesis of the double-layer membrane that constitutes the autophagosome vesicle, responsible for delivering the cargo from the cytoplasm to the vacuole lumen. The contributions of Atg-related proteins in the pathogenic yeast in the genus Cryptococcus remain to be explored, to elucidate the molecular basis of the autophagy pathway. In this context, we aimed to investigate the role of autophagy-related proteins 4 and 8 (Atg4 and Atg8) during autophagy induction and their contribution with non-autophagic events in C. neoformans. We found that Atg4 and Atg8 are conserved proteins and that they interact physically with each other. ATG gene deletions resulted in cells sensitive to nitrogen starvation. ATG4 gene disruption affects Atg8 degradation and its translocation to the vacuole lumen, after autophagy induction. Both atg4 and atg8 mutants are more resistant to oxidative stress, have an impaired growth in the presence of the cell wall-perturbing agent Congo Red, and are sensitive to the proteasome inhibitor bortezomib (BTZ). By that, we conclude that in C. neoformans the autophagy-related proteins Atg4 and Atg8 play an important role in the autophagy pathway; which are required for autophagy regulation, maintenance of amino acid levels and cell adaptation to stressful conditions. Public Library of Science 2020-04-06 /pmc/articles/PMC7135279/ /pubmed/32251488 http://dx.doi.org/10.1371/journal.pone.0230981 Text en © 2020 Roberto et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Roberto, Thiago Nunes
Lima, Ricardo Ferreira
Pascon, Renata Castiglioni
Idnurm, Alexander
Vallim, Marcelo Afonso
Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans
title Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans
title_full Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans
title_fullStr Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans
title_full_unstemmed Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans
title_short Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans
title_sort biological functions of the autophagy-related proteins atg4 and atg8 in cryptococcus neoformans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135279/
https://www.ncbi.nlm.nih.gov/pubmed/32251488
http://dx.doi.org/10.1371/journal.pone.0230981
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