Mitochondrial outer-membrane E3 ligase MUL1 ubiquitinates ULK1 and regulates selenite-induced mitophagy
Mitochondrial outer-membrane E3 ligase MUL1 ubiquitinates ULK1 and regulates selenite-induced mitophagy
复制标题
线粒体外膜 E3 连接酶 MUL1 泛素化 ULK1 并调节亚硒酸盐诱导的线粒体自噬
DOI：
10.1080/15548627.2015.1017180
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发表时间：
2015-08-01
期刊：
影响因子：
13.3
通讯作者：
Zhu, Yushan
中科院分区：
文献类型：
--
作者：
Li, Jie;Qi, Wei;Zhu, Yushan
线粒体是调节自噬的膜来源和信号平台。越来越多的证据还表明，在线粒体和氧化应激下，受损的线粒体可以通过选择性有丝分裂吞噬和一般自噬来移除。通过线粒体E3连接酶实现的蛋白质泛素化在线粒体外膜蛋白降解、线粒体动力学和有丝分裂中起着综合作用。在这里，我们证明了MUL1，一个线粒体定位的E3连接酶，以ATG5和ULK1依赖的方式调节亚硒诱导的有丝分裂吞噬。亚硒处理后，ULK1部分移位到线粒体，并与MUL1相互作用。我们还证明了ULK1是MUL1的一种新型底物。这些结果提示线粒体与自噬调节有关，并为硒作为化学预防药物的有益作用提供了新的机制。
Mitochondria serve as membrane sources and signaling platforms for regulating autophagy. Accumulating evidence has also shown that damaged mitochondria are removed through both selective mitophagy and general autophagy in response to mitochondrial and oxidative stresses. Protein ubiquitination through mitochondrial E3 ligases plays an integrative role in mitochondrial outer membrane protein degradation, mitochondrial dynamics, and mitophagy. Here we showed that MUL1, a mitochondria-localized E3 ligase, regulates selenite-induced mitophagy in an ATG5 and ULK1-dependent manner. ULK1 partially translocated to mitochondria after selenite treatment and interacted with MUL1. We also demonstrated that ULK1 is a novel substrate of MUL1. These results suggest the association of mitochondria with autophagy regulation and provide a new mechanism for the beneficial effects of selenium as a chemopreventive agent.