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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Roberto, Thiago Nunes [1] ; Lima, Ricardo Ferreira [2] ; Pascon, Renata Castiglioni [1] ; Idnurm, Alexander [3] ; Vallim, Marcelo Afonso [1]
Total Authors: 5
Affiliation:
[1] Univ Fed Sao Paulo, Dept Ciencias Biol, Diadema, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Infectol, Sao Paulo, SP - Brazil
[3] Univ Melbourne, Sch BioSci, Melbourne, Vic - Australia
Total Affiliations: 3
Document type: Journal article
Source: PLoS One; v. 15, n. 4 APR 6 2020.
Web of Science Citations: 1
Abstract

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. (AU)

FAPESP's process: 16/50185-5 - The role of autophagy on the pathogenicity of Cryptococcus neoformans and as a potential drug target
Grantee:Marcelo Afonso Vallim
Support Opportunities: Regular Research Grants
FAPESP's process: 16/14542-8 - Genetic characterization of the regulatory elements of the biosynthesis and uptake of amino acids and their role in virulence of Cryptococcus neoformans.
Grantee:Renata Castiglioni Pascon
Support Opportunities: Regular Research Grants
FAPESP's process: 15/04400-9 - The role of autophagy in Cryptococcus neorformas high temperature (37°C) growth and virulence
Grantee:Marcelo Afonso Vallim
Support Opportunities: Regular Research Grants