Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation
Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation
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DOI：
10.4161/auto.25832
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发表时间：
2013-10-01
期刊：
影响因子：
13.3
通讯作者：
Langsley, Gordon
中科院分区：
文献类型：
--
作者：
Tomlins, Andrew M.;Ben-Rached, Fathia;Langsley, Gordon
氨基酸的利用对人类疟原虫恶性疟原虫红细胞阶段的生长很重要，然而，在限制氨基酸供应的条件下，允许疟原虫存活的分子机制尚不清楚。我们在这里提供的数据表明，尽管缺乏典型的溶酶体来消化自噬体，恶性疟原虫的自噬途径仍起作用。它涉及到PfATG8，它有一个c端甘氨酸这是蛋白质与自噬体结合所必需的。氨基酸饥饿导致PfATG8-和pfrab7标记的囊泡之间共定位增加，并导致与pfrab7介导的PfATG8阳性自噬体成熟一致的共标记结构酸化；这是一个促进寄生虫生存的快速过程。免疫电镜分析检测到PfRAB7和PfATG8存在于双膜结合的囊泡上，也存在于寄生虫食物液泡附近或内部，这与自噬体在进入食物液泡消化之前与内体系统融合一致。在非饥饿的寄生虫中，当细胞器的形成被破坏时，在完整的顶质体膜上、顶质体靶向囊泡和顶质体残体上发现了PfATG8，而不是PfRAB7；定位也需要c端甘氨酸。这些发现表明，PfATG8除了在涉及pfrab7 -内体系统和食物液泡的自噬中发挥经典作用外，还与顶质体靶向囊泡和成熟的顶质体有关，因此有助于顶质体的形成和维持。因此，除了形成经典自噬所需的自噬体外，PfATG8可能还具有这种第二种作用。
Amino acid utilization is important for the growth of the erythrocytic stages of the human malaria parasite Plasmodium falciparum, however the molecular mechanism that permits survival of the parasite during conditions of limiting amino acid supply is poorly understood. We provide data here suggesting that an autophagy pathway functions in P. falciparum despite the absence of a typical lysosome for digestion of the autophagosomes. It involves PfATG8, which has a C-terminal glycine which is absolutely required for association of the protein with autophagosomes. Amino acid starvation provoked increased colocalization between PfATG8- and PfRAB7-labeled vesicles and acidification of the colabeled structures consistent with PfRAB7-mediated maturation of PfATG8-positive autophagosomes; this is a rapid process facilitating parasite survival. Immuno-electron microscopic analyses detected PfRAB7 and PfATG8 on double-membrane-bound vesicles and also near or within the parasite's food vacuole, consistent with autophagosomes fusing with the endosomal system before being routed to the food vacuole for digestion. In nonstarved parasites, PfATG8, but not PfRAB7, was found on the intact apicoplast membrane and on apicoplast-targeted vesicles and apicoplast remnants when the formation of the organelle was disrupted; a localization also requiring the C-terminal glycine. These findings suggest that in addition to a classical role in autophagy, which involves the PfRAB7-endosomal system and food vacuole, PfATG8 is associated with apicoplast-targeted vesicles and the mature apicoplast, and as such contributes to apicoplast formation and maintenance. Thus, PfATG8 may be unique in having such a second role in addition to the formation of autophagosomes required for classical autophagy.