MoVast2 combined with MoVast1 regulates lipid homeostasis and autophagy in Magnaporthe oryzae
MoVast2 combined with MoVast1 regulates lipid homeostasis and autophagy in Magnaporthe oryzae
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DOI：
10.1080/15548627.2023.2181739
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发表时间：
2023-02-27
期刊：
影响因子：
13.3
通讯作者：
Lin，Fu-Cheng
中科院分区：
文献类型：
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作者：
Zhu，Xue-Ming;Li，Lin;Lin，Fu-Cheng
巨噬/自噬是真核生物中一个进化保守的生物过程，它降解不需要的物质，如蛋白质聚集体、受损的线粒体甚至病毒，以维持细胞存活。我们之前的研究表明，MoVast1作为自噬调节因子，调节稻瘟病菌的自噬、膜张力和甾醇稳态。然而，自噬与VASt结构域蛋白之间的详细调控关系仍未得到解决。本研究中，我们发现了另一个含有VASt结构域的蛋白MoVast2，并进一步揭示了MoVast2在m中的调控机制。oryzae。MoVast2与MoVast1和moat8相互作用，并在PAS上共定位，删除MoVast2会导致不适当的自噬进展。通过TOR活性分析、甾醇和鞘脂含量检测，我们发现ΔMovast2mutant中甾醇含量较高，而该突变体鞘脂含量较低，TORC1和TORC2活性较低。此外，MoVast2与MoVast1进行了共定位。movast1缺失突变体中MoVast2定位正常；然而，删除movast2会导致MoVast1定位错误。值得注意的是，宽靶点脂质组学分析揭示了ΔMovast2mutant中主要PM成分甾醇和鞘脂的显著变化，这些成分参与脂质代谢和自噬途径。这些发现证实了MoVast1的功能受到MoVast2的调节，揭示了MoVast2联合MoVast1通过调节m内TOR活性来维持脂质稳态和自噬平衡。oryzae。
Macroautophagy/autophagy is an evolutionarily conserved biological process among eukaryotes that degrades unwanted materials such as protein aggregates, damaged mitochondria and even viruses to maintain cell survival. Our previous studies have demonstrated that MoVast1 acts as an autophagy regulator regulating autophagy, membrane tension, and sterol homeostasis in rice blast fungus. However, the detailed regulatory relationships between autophagy and VASt domain proteins remain unsolved. Here, we identified another VASt domain-containing protein, MoVast2, and further uncovered the regulatory mechanism of MoVast2 inM. oryzae. MoVast2 interacted with MoVast1 and MoAtg8, and colocalized at the PAS and deletion ofMoVAST2results in inappropriate autophagy progress. Through TOR activity analysis, sterols and sphingolipid content detection, we found high sterol accumulation in the ΔMovast2mutant, whereas this mutant showed low sphingolipids and low activity of both TORC1 and TORC2. In addition, MoVast2 colocalized with MoVast1. The localization of MoVast2 in theMoVAST1deletion mutant was normal; however, deletion ofMoVAST2leads to mislocalization of MoVast1. Notably, the wide-target lipidomic analyses revealed significant changes in sterols and sphingolipids, the major PM components, in the ΔMovast2mutant, which was involved in lipid metabolism and autophagic pathways. These findings confirmed that the functions of MoVast1 were regulated by MoVast2, revealing that MoVast2 combined with MoVast1 maintained lipid homeostasis and autophagy balance by regulating TOR activity inM. oryzae.