Starvation-response may not involve Atg1-dependent autophagy induction in non-unikont parasites.
Starvation-response may not involve Atg1-dependent autophagy induction in non-unikont parasites.
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DOI：
10.1038/srep05829
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发表时间：
2014-07-25
影响因子：
4.6
通讯作者：
Vellai T
中科院分区：
文献类型：
--
作者：
Földvári-Nagy L;Ari E;Csermely P;Korcsmáros T;Vellai T
自噬是溶酶体介导的自我降解过程，与酵母、网骨藻和动物在饥饿期间的存活有关。在这些真核生物分类群（统称为Unikonts）中，自噬主要通过Atg 1/ULK 1复合物诱导，以响应营养素耗尽。自噬在非单鞭毛寄生虫中也得到了很好的研究，如锥虫和疟原虫，并发现在其生命周期的转变中很重要。然而，自噬是如何在非unikonts诱导仍然在很大程度上未被揭示。使用生物信息学的方法，我们研究了存在的Atg 1及其复杂的基因组中的40个非unikonts。我们发现这些基因组不编码典型的Atg 1蛋白：BLAST和HMMER查询仅与Atg 1的激酶结构域匹配，而负责调节和蛋白结合的其他片段缺失。非unikonts也缺乏其他组件的Atg 1诱导复合物。另一种自噬诱导剂Atg 6的直系同源物仅在一半物种中发现，表明另一半可能具有其他诱导机制。由于关键的自噬基因在生命周期中具有不同的表达模式，我们提出了这些原生生物中自噬主要在转录后水平诱导的可能性。了解这些寄生虫中的Atg 1独立自噬诱导机制可能会导致新的药理学干预，而不会影响人类Atg 1依赖性自噬。
Autophagy, the lysosome-mediated self-degradation process, is implicated in survival during starvation in yeast, Dictyostelium and animals. In these eukaryotic taxa (collectively called Unikonts), autophagy is induced primarily through the Atg1/ULK1 complex in response to nutrient depletion. Autophagy has also been well-studied in non-unikont parasites, such as Trypanosoma and Plasmodium, and found important in their life-cycle transitions. However, how autophagy is induced in non-unikonts remains largely unrevealed. Using a bioinformatics approach, we examined the presence of Atg1 and of its complex in the genomes of 40 non-unikonts. We found that these genomes do not encode typical Atg1 proteins: BLAST and HMMER queries matched only with the kinase domain of Atg1, while other segments responsible for regulation and protein-binding were missing. Non-unikonts also lacked other components of the Atg1-inducing complex. Orthologs of an alternative autophagy inducer, Atg6 were found only in the half of the species, indicating that the other half may possess other inducing mechanisms. As key autophagy genes have differential expression patterns during life-cycle, we raise the possibility that autophagy in these protists is induced mainly at the post-transcriptional level. Understanding Atg1-independent autophagy induction mechanisms in these parasites may lead to novel pharmacological interventions, not affecting human Atg1-dependent autophagy.