Glycosome turnover in Leishmania major is mediated by autophagy.
Glycosome turnover in Leishmania major is mediated by autophagy.
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DOI：
10.4161/auto.36438
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发表时间：
2014
期刊：
影响因子：
13.3
通讯作者：
Mottram JC
中科院分区：
文献类型：
--
作者：
Cull B;Prado Godinho JL;Fernandes Rodrigues JC;Frank B;Schurigt U;Williams RA;Coombs GH;Mottram JC
自噬是利什曼原虫分化过程中发生的细胞重塑背后的核心过程，但原生动物寄生虫的自噬体的货物尚不清楚。我们已经鉴定出糖体，即过氧化物酶体样细胞器，它们独特地将利什曼原虫和其他动质体寄生原生动物中的糖酵解酶和其他代谢酶区分开来，作为自噬体货物。有人提出，糖体的数量及其含量在利什曼原虫生命周期中发生变化，这是适应所遇到的不同环境的关键。 RFP-SQL 标记的糖体定量表明，L.major 的前鞭毛体每个细胞拥有~20 个糖体，而无鞭毛体则包含~10 个糖体。自噬缺陷型 L. Major Δatg5 突变体的前鞭毛体和无鞭毛体中糖体数量显着增加，这表明自噬参与糖体稳态，并为之前观察到的这些突变体的生长和毒力缺陷提供了部分解释。使用 GFP-ATG8 标记自噬体表明糖体是其中约 15% 的货物；含有糖体的自噬体被运输到溶酶体进行降解。在分化过程中自噬体的数量增加了10倍，但含有糖体的自噬体的百分比保持不变。这表明糖体周转率的增加是由于自噬的总体增加，而不是含有该货物的自噬体的上调。在正常生长或分化期间，未观察到大型乳杆菌中单个线粒体的线粒体自噬；然而，应激诱导的断裂产生的线粒体残余物与自噬体和溶酶体共定位，表明自噬用于回收这些受损的细胞器。这些数据表明，利什曼原虫的自噬不仅在维持细胞稳态和回收受损细胞器方面发挥着核心作用，而且在通过糖体更新适应环境变化方面也发挥着至关重要的作用。
Autophagy is a central process behind the cellular remodeling that occurs during differentiation of Leishmania, yet the cargo of the protozoan parasite's autophagosome is unknown. We have identified glycosomes, peroxisome-like organelles that uniquely compartmentalize glycolytic and other metabolic enzymes in Leishmania and other kinetoplastid parasitic protozoa, as autophagosome cargo. It has been proposed that the number of glycosomes and their content change during the Leishmania life cycle as a key adaptation to the different environments encountered. Quantification of RFP-SQL-labeled glycosomes showed that promastigotes of L. major possess ∼20 glycosomes per cell, whereas amastigotes contain ∼10. Glycosome numbers were significantly greater in promastigotes and amastigotes of autophagy-defective L. major Δatg5 mutants, implicating autophagy in glycosome homeostasis and providing a partial explanation for the previously observed growth and virulence defects of these mutants. Use of GFP-ATG8 to label autophagosomes showed glycosomes to be cargo in ∼15% of them; glycosome-containing autophagosomes were trafficked to the lysosome for degradation. The number of autophagosomes increased 10-fold during differentiation, yet the percentage of glycosome-containing autophagosomes remained constant. This indicates that increased turnover of glycosomes was due to an overall increase in autophagy, rather than an upregulation of autophagosomes containing this cargo. Mitophagy of the single mitochondrion was not observed in L. major during normal growth or differentiation; however, mitochondrial remnants resulting from stress-induced fragmentation colocalized with autophagosomes and lysosomes, indicating that autophagy is used to recycle these damaged organelles. These data show that autophagy in Leishmania has a central role not only in maintaining cellular homeostasis and recycling damaged organelles but crucially in the adaptation to environmental change through the turnover of glycosomes.