Abstract
Toxoplasma gondii is a parasitic protist possessing a limited set of proteins involved in the autophagy pathway, a self-degradative machinery for protein and organelle recycling. This distant eukaryote has even repurposed part of this machinery, centered on protein ATG8, for a non-degradative function related to the maintenance of the apicoplast, a parasite-specific organelle. However, some evidence also suggest Toxoplasma is able to generate autophagic vesicles upon stress, and that some autophagy-related proteins, such as ATG9, might be involved solely in the canonical autophagy function. Here, we have characterised TgPROP1 and TgPROP2, two Toxoplasma proteins containing WD-40 repeat that can bind lipids for their recruitment to vesicular structures upon stress. They belong to the PROPPIN family and are homologues to ATG18/WIPI, which are known to be important for the autophagic process. We conducted a functional analysis of these two Toxoplasma PROPPINs. One of them is dispensable for normal in vitro growth, although it may play a role for parasite survival in specific stress conditions or for parasite fitness in the host, through a canonical autophagy-related function. The other, however, seems important for parasite viability in normal growth conditions and could be primarily involved in a non-canonical function. These divergent roles for two proteins from the same family illustrate the functional versatility of the autophagy-related machinery in Toxoplasma.
Highlights
IntroductionMacroautophagy ( referred to as autophagy hereafter), is a life-promoting lysosomal degradation pathway required for maintaining cellular homeostasis and surviving external stresses such as periods of nutrient deprivation [1]
Macroautophagy, is a life-promoting lysosomal degradation pathway required for maintaining cellular homeostasis and surviving external stresses such as periods of nutrient deprivation [1]
We performed homology searches in the T. gondii genomic database using Atg18 from Saccharomyces cerevisiae as a query, and we identified two putative homologues: TGGT1_288600 and TGGT1_220160 (Fig 1A)
Summary
Macroautophagy ( referred to as autophagy hereafter), is a life-promoting lysosomal degradation pathway required for maintaining cellular homeostasis and surviving external stresses such as periods of nutrient deprivation [1]. This process allows the degradation and recycling of cellular components through their segregation into multi-membrane vesicles called autophagosomes, which will eventually fuse with lysosomes. The understanding of the molecular processes underlying autophagy was revolutionised by the discovery of so-called. Two Toxoplasma PROPPINs involved in different cellular functions. Foundation of China (81672052), the Zhejiang Natural Science Funds for Distinguished Young Scientists (LR17H190001) and Zhejiang Xinmiao talent plan (2017R413062). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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