Transient Contraction of Mitochondria Induces Depolarization through the Inner Membrane Dynamin OPA1 Protein
Transient Contraction of Mitochondria Induces Depolarization through the Inner Membrane Dynamin OPA1 Protein
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DOI：
10.1074/jbc.m113.533299
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发表时间：
2014-04-25
影响因子：
4.8
通讯作者：
Yoon, Yisang
中科院分区：
文献类型：
--
作者：
Lee, Hakjoo;Yoon, Yisang
背景：丝状线粒体内膜电位同时波动提示电和功能联系。结果：线粒体基质瞬间收缩通过细胞膜融合动力蛋白OPA1诱导去极化。结论：线粒体短暂性收缩是一种以前未被认识到的细胞机制。意义：线粒体瞬间形态收缩是一种调节线粒体活性的新机制。动力蛋白相关的膜重塑蛋白通过介导分裂和融合调节线粒体形态。虽然线粒体形态被认为是维持线粒体功能的重要因素，但线粒体形态与功能之间的直接机制联系尚未明确。我们在这里报告了一个以前未被识别的线粒体基质短暂收缩的细胞过程。重要的是，我们发现线粒体的这种短暂形态收缩伴随着可逆的内膜电位损失或减少。裂变缺陷极大地放大了这一现象，在功能上表现为内膜质子泄漏的增加。我们发现，电子传递活动是线粒体形态收缩的必要条件。此外，我们发现，在裂变缺陷中沉默内膜相关动力蛋白视神经萎缩1 （OPA1）可以防止线粒体去极化和减少质子泄漏，而不会阻断线粒体收缩，这表明OPA1是将基质收缩与线粒体去极化耦合的一个因素。我们的研究结果表明，瞬态基质收缩是一种新的细胞机制，通过细胞膜动力蛋白OPA1的功能调节线粒体活性。
Background: Simultaneous fluctuation of the inner membrane potential in filamentous mitochondria suggests electrical and functional connection. Results: Transient contraction of mitochondrial matrix induces depolarization through the inner membrane fusion dynamin OPA1. Conclusion: Transient mitochondrial contraction is a previously unrecognized cellular mechanism that induces depolarization. Significance: Transient morphological contraction of mitochondria represents a new mechanism regulating mitochondrial activity.Dynamin-related membrane remodeling proteins regulate mitochondrial morphology by mediating fission and fusion. Although mitochondrial morphology is considered an important factor in maintaining mitochondrial function, a direct mechanistic link between mitochondrial morphology and function has not been defined. We report here a previously unrecognized cellular process of transient contraction of the mitochondrial matrix. Importantly, we found that this transient morphological contraction of mitochondria is accompanied by a reversible loss or decrease of inner membrane potential. Fission deficiency greatly amplified this phenomenon, which functionally exhibited an increase of inner membrane proton leak. We found that electron transport activity is necessary for the morphological contraction of mitochondria. Furthermore, we discovered that silencing the inner membrane-associated dynamin optic atrophy 1 (OPA1) in fission deficiency prevented mitochondrial depolarization and decreased proton leak without blocking mitochondrial contraction, indicating that OPA1 is a factor in coupling matrix contraction to mitochondrial depolarization. Our findings show that transient matrix contraction is a novel cellular mechanism regulating mitochondrial activity through the function of the inner membrane dynamin OPA1.