The GET pathway can increase the risk of mitochondrial outer membrane proteins to be mistargeted to the ER
The GET pathway can increase the risk of mitochondrial outer membrane proteins to be mistargeted to the ER
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DOI：
10.1242/jcs.211110
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发表时间：
2018-05-15
影响因子：
4
通讯作者：
Rapaport, Doron
中科院分区：
文献类型：
--
作者：
Vitali, Daniela G.;Sinzel, Monika;Rapaport, Doron
尾锚定（TA）蛋白通过其C末端的单个跨膜区段（TMS）锚定至其相应的膜。在酵母中，TA蛋白靶向内质网（ER）可以通过引导进入TA蛋白（GET）途径介导，而线粒体TA蛋白如何靶向其目的地尚不清楚。已经广泛观察到，一些线粒体外膜（ORM）蛋白在过表达或当它们的靶向信号被掩蔽时被错误地定位到ER。然而，这种错误分类的机制目前尚不清楚。在这项研究中，我们证明了GET机制的参与，在错误的次优EMPREPTORS蛋白ER。这些发现表明，GET机制可以，原则上，识别和指导线粒体和非经典TA蛋白。因此，在正常条件下，必须存在一个主动的线粒体靶向途径，该途径在与其他途径的动力学竞争中占主导地位。
Tail-anchored (TA) proteins are anchored to their corresponding membrane via a single transmembrane segment (TMS) at their C-terminus. In yeast, the targeting of TA proteins to the endoplasmic reticulum (ER) can be mediated by the guided entry of TA proteins (GET) pathway, whereas it is not yet clear how mitochondrial TA proteins are targeted to their destination. It has been widely observed that some mitochondrial outer membrane (MOM) proteins are mistargeted to the ER when overexpressed or when their targeting signal is masked. However, the mechanism of this erroneous sorting is currently unknown. In this study, we demonstrate the involvement of the GET machinery in the mistargeting of suboptimal MOM proteins to the ER. These findings suggest that the GET machinery can, in principle, recognize and guide mitochondrial and non-canonical TA proteins. Hence, under normal conditions, an active mitochondrial targeting pathway must exist that dominates the kinetic competition against other pathways.