Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
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DOI：
10.7554/elife.50973
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发表时间：
2020-01-10
期刊：
影响因子：
7.7
通讯作者：
Chao, Luke H.
中科院分区：
文献类型：
--
作者：
Ge, Yifan;Shi, Xiaojun;Chao, Luke H.
线粒体膜动力学是一个细胞变阻器，它与代谢功能和细胞器形态有关。使用体外重建系统，我们描述了一种机制，如何线粒体内膜融合的比例调节两种形式的Opa 1。我们发现，长型Opa 1（l-Opa 1）是足够的膜对接，半融合和低水平的内容物释放。然而，化学计量水平的加工过的短形式Opa 1（s-Opa 1）与l-Opa 1一起起作用以介导有效和快速的膜孔打开。此外，我们发现过量的s-Opa 1抑制融合活性，如在蛋白质稳态改变的条件下所见。这些观察描述了门控膜融合的机制。
Mitochondrial membrane dynamics is a cellular rheostat that relates metabolic function and organelle morphology. Using an in vitro reconstitution system, we describe a mechanism for how mitochondrial inner-membrane fusion is regulated by the ratio of two forms of Opa1. We found that the long-form of Opa1 (l-Opa1) is sufficient for membrane docking, hemifusion and low levels of content release. However, stoichiometric levels of the processed, short form of Opa1 (s-Opa1) work together with l-Opa1 to mediate efficient and fast membrane pore opening. Additionally, we found that excess levels of s-Opa1 inhibit fusion activity, as seen under conditions of altered proteostasis. These observations describe a mechanism for gating membrane fusion.