Specific requirements of nonbilayer phospholipids in mitochondrial respiratory chain function and formation.
Specific requirements of nonbilayer phospholipids in mitochondrial respiratory chain function and formation.
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DOI：
10.1091/mbc.e15-12-0865
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发表时间：
2016-07-15
影响因子：
3.3
通讯作者：
Gohil VM
中科院分区：
文献类型：
--
作者：
Baker CD;Basu Ball W;Pryce EN;Gohil VM
磷脂酰乙醇胺（PE）和心磷脂在线粒体呼吸链超复合物的活性和组装中分别具有特定的作用，而磷脂酰胆碱是多余的。非线粒体PE可以被转运到线粒体中，在那里它可以完全替代线粒体PE生物合成的缺乏。线粒体膜磷脂组成通过影响线粒体呼吸链（MRC）复合物组装成超复合物来影响线粒体功能。例如，心磷脂（CL）（线粒体的标志性非双层形成磷脂）的损失导致MRC超复合物的破坏。然而，最丰富的线粒体磷脂，双层形成磷脂酰胆碱（PC）和非双层形成磷脂酰乙醇胺（PE）的功能，并没有明确的定义。使用酵母突变体的PE和PC的生物合成途径，我们表现出一个特定的要求线粒体PE在MRC复合物III和IV的活动，但不为他们的形成，而PC的损失不影响MRC的功能或形成。与CL不同，MRC超复合物的形成不需要线粒体PE或PC，这强调了CL在超复合物组装中的特定要求。有趣的是，在内质网（ER）中生物合成的PE可以在功能上替代线粒体PE生物合成的缺乏，这表明存在从ER到线粒体的PE转运途径。为了了解PE运输的机制，我们破坏了ERMES复合物形成的ER-线粒体接触位点，发现ERMES虽然对PE运输不是必需的，但有助于有效地拯救线粒体PE缺乏症。我们的工作突出了非双层形成磷脂在MRC功能和形成中的特定作用。
Phosphatidylethanolamine (PE) and cardiolipin have specific roles in the activity and assembly of the mitochondrial respiratory chain supercomplexes, respectively, whereas phosphatidylcholine is redundant. Nonmitochondrial PE can be transported into mitochondria, where it can fully substitute for the lack of mitochondrial PE biosynthesis. Mitochondrial membrane phospholipid composition affects mitochondrial function by influencing the assembly of the mitochondrial respiratory chain (MRC) complexes into supercomplexes. For example, the loss of cardiolipin (CL), a signature non–bilayer-forming phospholipid of mitochondria, results in disruption of MRC supercomplexes. However, the functions of the most abundant mitochondrial phospholipids, bilayer-forming phosphatidylcholine (PC) and non–bilayer-forming phosphatidylethanolamine (PE), are not clearly defined. Using yeast mutants of PE and PC biosynthetic pathways, we show a specific requirement for mitochondrial PE in MRC complex III and IV activities but not for their formation, whereas loss of PC does not affect MRC function or formation. Unlike CL, mitochondrial PE or PC is not required for MRC supercomplex formation, emphasizing the specific requirement of CL in supercomplex assembly. Of interest, PE biosynthesized in the endoplasmic reticulum (ER) can functionally substitute for the lack of mitochondrial PE biosynthesis, suggesting the existence of PE transport pathway from ER to mitochondria. To understand the mechanism of PE transport, we disrupted ER–mitochondrial contact sites formed by the ERMES complex and found that, although not essential for PE transport, ERMES facilitates the efficient rescue of mitochondrial PE deficiency. Our work highlights specific roles of non–bilayer-forming phospholipids in MRC function and formation.