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PMID: 22144900 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and for normal intracellular development of Toxoplasma gondii tachyzoites.

PLoS pathogens ·Vol. 7 ·No. 12 ·2011-12-00 ·Pages e1002416

Besteiro S, Brooks CF, Striepen B, Dubremetz JF

Abstract

Autophagy is a cellular process that is highly conserved among eukaryotes and permits the degradation of cellular material. Autophagy is involved in multiple survival-promoting processes. It not only facilitates the maintenance of cell homeostasis by degrading long-lived proteins and damaged organelles, but it also plays a role in cell differentiation and cell development. Equally important is its function for survival in stress-related conditions such as recycling of proteins and organelles during nutrient starvation. Protozoan parasites have complex life cycles and face dramatically changing environmental conditions; whether autophagy represents a critical coping mechanism throughout these changes remains poorly documented. To investigate this in Toxoplasma gondii, we have used TgAtg8 as an autophagosome marker and showed that autophagy and the associated cellular machinery are present and functional in the parasite. In extracellular T. gondii tachyzoites, autophagosomes were induced in response to amino acid starvation, but they could also be observed in culture during the normal intracellular development of the parasites. Moreover, we generated a conditional T. gondii mutant lacking the orthologue of Atg3, a key autophagy protein. TgAtg3-depleted parasites were unable to regulate the conjugation of TgAtg8 to the autophagosomal membrane. The mutant parasites also exhibited a pronounced fragmentation of their mitochondrion and a drastic growth phenotype. Overall, our results show that TgAtg3-dependent autophagy might be regulating mitochondrial homeostasis during cell division and is essential for the normal development of T. gondii tachyzoites.

MeSH Terms
Cell Division/physiology Cells, Cultured Fibroblasts/parasitology Humans Male Mitochondria/genetics,metabolism,ultrastructure Mutation Protozoan Proteins/genetics,metabolism Toxoplasma/genetics,metabolism,ultrastructure Toxoplasmosis/genetics,metabolism,pathology Ubiquitin-Conjugating Enzymes/genetics,metabolism
Chemicals
Protozoan Proteins Ubiquitin-Conjugating Enzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Besteiro Sébastien
UMR 5235 CNRS, Universités de Montpellier 2 et 1, Dynamique des Interactions Membranaires Normales et Pathologiques, Montpellier, France. sebastien.besteiro@univ-montp2.fr
Brooks Carrie F
Striepen Boris
Dubremetz Jean-François
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Article Info
Journal
PLoS pathogens
Abbr.
PLoS Pathog
ISSN
1553-7374
DOI
10.1371/journal.ppat.1002416
Email
sebastien.besteiro@univ-montp2.fr
Published
2011-12-00
Epub
2011-00-01
Pages
e1002416
Language
English
Region
United States
NLM ID
101238921
PMCID
PMC3228817
Subset
IM
Grants
NIAID NIH HHS · R01 AI064671 · United States
External Links
PubMed source DOI: 10.1371/journal.ppat.1002416 PMC Full Text View journal details
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