MAVS maintains mitochondrial homeostasis via autophagy.
MAVS maintains mitochondrial homeostasis via autophagy.
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DOI：
10.1038/celldisc.2016.24
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发表时间：
2016
期刊：
影响因子：
33.5
通讯作者：
Sun Q
中科院分区：
文献类型：
--
作者：
Sun X;Sun L;Zhao Y;Li Y;Lin W;Chen D;Sun Q
线粒体抗病毒信号蛋白（MAVS）通过与活化的rig - 1和MDA5受体物理相互作用，作为一种关键的转导抗病毒信号的衔接蛋白。MAVS在线粒体外膜执行其功能，调节下游抗病毒信号传导，表明线粒体为先天抗病毒信号转导提供了功能平台。然而，对于mavs介导的抗病毒信号是否以及如何促进线粒体稳态，人们知之甚少。在这里，我们表明MAVS的激活足以诱导自噬信号，这可能介导受损线粒体的周转。重要的是，我们发现MAVS通过其LC3结合基序“YxxI”直接与LC3相互作用，这表明MAVS可能作为自噬受体，在RLR信号过度激活时介导线粒体周转。此外，我们提供的证据表明，MAVS自聚集及其与TRAF2/6蛋白的相互作用对MAVS介导的线粒体周转很重要。总的来说，我们的研究结果表明MAVS作为线粒体相关自噬信号的潜在受体来维持线粒体稳态。
Mitochondrial antiviral signalling protein (MAVS) acts as a critical adaptor protein to transduce antiviral signalling by physically interacting with activated RIG-I and MDA5 receptors. MAVS executes its functions at the outer membrane of mitochondria to regulate downstream antiviral signalling, indicating that the mitochondria provides a functional platform for innate antiviral signalling transduction. However, little is known about whether and how MAVS-mediated antiviral signalling contributes to mitochondrial homeostasis. Here we show that the activation of MAVS is sufficient to induce autophagic signalling, which may mediate the turnover of the damaged mitochondria. Importantly, we find MAVS directly interacts with LC3 through its LC3-binding motif ‘YxxI’, suggesting that MAVS might act as an autophagy receptor to mediate mitochondrial turnover upon excessive activation of RLR signalling. Furthermore, we provide evidence that both MAVS self-aggregation and its interaction with TRAF2/6 proteins are important for MAVS-mediated mitochondrial turnover. Collectively, our findings suggest that MAVS acts as a potential receptor for mitochondria-associated autophagic signalling to maintain mitochondrial homeostasis.