Raturi Arun, Simmen Thomas
Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
Biochim Biophys Acta. 2013 Jan;1833(1):213-24. doi: 10.1016/j.bbamcr.2012.04.013. Epub 2012 May 2.
More than a billion years ago, bacterial precursors of mitochondria became endosymbionts in what we call eukaryotic cells today. The true significance of the word "endosymbiont" has only become clear to cell biologists with the discovery that the endoplasmic reticulum (ER) superorganelle dedicates a special domain for the metabolic interaction with mitochondria. This domain, identified in all eukaryotic cell systems from yeast to man and called the mitochondria-associated membrane (MAM), has a distinct proteome, specific tethers on the cytosolic face and regulatory proteins in the ER lumen of the ER. The MAM has distinct biochemical properties and appears as ER tubules closely apposed to mitochondria on electron micrographs. The functions of the MAM range from lipid metabolism and calcium signaling to inflammasome formation. Consistent with these functions, the MAM is enriched in lipid metabolism enzymes and calcium handling proteins. During cellular stress situations, like an altered cellular redox state, the MAM alters its set of regulatory proteins and thus alters MAM functions. Notably, this set prominently comprises ER chaperones and oxidoreductases that connect protein synthesis and folding inside the ER to mitochondrial metabolism. Moreover, ER membranes associated with mitochondria also accommodate parts of the machinery that determines mitochondrial membrane dynamics and connect mitochondria to the cytoskeleton. Together, these exciting findings demonstrate that the physiological interactions between the ER and mitochondria are so bilateral that we are tempted to compare their relationship to the one of a married couple: distinct, but inseparable and certainly dependent on each other. In this paradigm, the MAM stands for the intracellular location where the two organelles tie the knot. Resembling "real life", the happy marriage between the two organelles prevents the onset of diseases that are characterized by disrupted metabolism and decreased lifespan, including neurodegeneration and cancer. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology.
超过十亿年前，线粒体的细菌前体在我们如今称为真核细胞的细胞中成为了内共生体。随着内质网（ER）这个超级细胞器为与线粒体进行代谢相互作用而专门划分出一个特殊区域这一发现的出现，细胞生物学家才真正明白“内共生体”这个词的真正意义。这个在从酵母到人类的所有真核细胞系统中都能识别出的区域，被称为线粒体相关膜（MAM），它拥有独特的蛋白质组、胞质面的特异性连接蛋白以及内质网腔中的调节蛋白。MAM具有独特的生化特性，在电子显微镜下呈现为与线粒体紧密相邻的内质网小管。MAM的功能涵盖从脂质代谢、钙信号传导到炎性小体形成等多个方面。与这些功能相一致，MAM富含脂质代谢酶和钙处理蛋白。在细胞应激状态下，比如细胞氧化还原状态改变时，MAM会改变其调节蛋白的组合，从而改变MAM的功能。值得注意的是，这一组合中显著包含将内质网内的蛋白质合成与折叠和线粒体代谢联系起来的内质网伴侣蛋白和氧化还原酶。此外，与线粒体相关的内质网膜还容纳了部分决定线粒体膜动态并将线粒体与细胞骨架相连的机制。总之，这些令人兴奋的发现表明内质网和线粒体之间的生理相互作用是如此双向，以至于我们不禁将它们的关系比作一对已婚夫妇：各自独立，但不可分割且相互依赖。在这个范例中，MAM代表了这两个细胞器结合的细胞内位置。就像“现实生活”一样，这两个细胞器的美满结合可预防以代谢紊乱和寿命缩短为特征的疾病的发生，包括神经退行性疾病和癌症。本文是名为“线粒体动力学与生理学”的特刊的一部分。
