Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and for normal intracellular development of Toxoplasma gondii tachyzoites.
Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and for normal intracellular development of Toxoplasma gondii tachyzoites.
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DOI：
10.1371/journal.ppat.1002416
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发表时间：
2011-12
期刊：
影响因子：
6.7
通讯作者：
Dubremetz JF
中科院分区：
文献类型：
--
作者：
Besteiro S;Brooks CF;Striepen B;Dubremetz JF
自噬是一种在真核生物中高度保守的细胞过程，允许细胞物质的降解。自噬参与多种生存促进过程。它不仅通过降解长寿命蛋白质和受损细胞器来促进细胞内稳态的维持，而且还在细胞分化和细胞发育中发挥作用。同样重要的是它在与压力相关的条件下的生存功能，例如在营养饥饿期间蛋白质和细胞器的再循环。原生动物寄生虫具有复杂的生命周期，并面临着急剧变化的环境条件;自噬是否代表了在这些变化中的关键应对机制仍然缺乏文献记载。为了在弓形虫中研究这一点，我们使用TgAtg 8作为自噬体标记，并表明自噬和相关的细胞机制在寄生虫中存在并发挥作用。在胞外T.在弓形虫速殖子中，自噬体被诱导响应于氨基酸饥饿，但它们也可以在寄生虫的正常细胞内发育过程中在培养物中观察到。此外，我们还生成了一个条件T。缺乏Atg 3（一种关键的自噬蛋白）直系同源物的弓形虫突变体。TgAtg 3耗尽的寄生虫不能调节TgAtg 8与自噬体膜的结合。突变体寄生虫也表现出显着的片段化，他们的寄生虫和急剧增长的表型。总的来说，我们的研究结果表明，TgAtg 3依赖的自噬可能在细胞分裂过程中调节线粒体的稳态，并且对T.弓形虫速殖子自噬是真核细胞中维持细胞内稳态的分解代谢过程，同时应对其不断变化的环境条件。从机制上讲，它也是一个相当复杂的过程，涉及多种蛋白质因子，并意味着许多蛋白质-蛋白质和蛋白质-膜相互作用。被自噬降解的细胞物质包含在一个被称为自噬体的膜结合区室中。我们的特点是在原生动物寄生虫弓形虫的自噬体的形成以下重新定位的自噬体结合TgAtg 8。因此，利用GFP-TgAtg 8作为标记，我们表明这是一个受调节的过程，并且可以通过氨基酸饥饿人为诱导。在正常分裂的细胞内寄生虫中也观察到自噬囊泡。耗尽弓形虫的TgAtg 3自噬蛋白导致TgAtg 8缀合至自噬体膜的损伤，并且在细胞水平上导致寄生虫的单个寄生虫的片段化和严重的生长停滞。因此，我们发现TgAtg 3依赖性自噬对于T细胞的正常细胞内发育是必不可少的。弓形虫速殖子
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. Autophagy is a catabolic process involved in maintaining cellular homeostasis in eukaryotic cells, while coping with their changing environmental conditions. Mechanistically, it is also a process of considerable complexity involving multiple protein factors and implying numerous protein-protein and protein-membrane interactions. The cellular material to be degraded by autophagy is contained in a membrane-bound compartment called the autophagosome. We have characterised the formation of autophagosomes in the protozoan parasite Toxoplasma gondii by following the relocalisation of autophagosome-bound TgAtg8. Thus, exploiting GFP-TgAtg8 as a marker, we showed that it is a process that is regulated and can be induced artificially by amino acid starvation. Autophagic vesicles were also observed in normally dividing intracellular parasites. Depleting Toxoplasma of the TgAtg3 autophagy protein led to an impairment of TgAtg8 conjugation to the autophagosomal membrane and, at the cellular level, to a fragmentation of the single mitochondrion of the parasite and to a severe growth arrest. We have thus found that TgAtg3-dependent autophagy is essential for normal intracellular development of T. gondii tachyzoites.
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影响因子：
3.7
作者：
Behnke MS;Wootton JC;Lehmann MM;Radke JB;Lucas O;Nawas J;Sibley LD;White MW
通讯作者：
White MW
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DOI：
10.1083/jcb.200112144
发表时间：
2002-05-13
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The Journal of cell biology
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影响因子：
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作者：
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通讯作者：
Ohsumi, Y
DOI：
10.1083/jcb.152.1.51
发表时间：
2001-01-08
期刊：
The Journal of cell biology
影响因子：
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