细胞亚器文献阅读之酵母液泡与线粒体的动态互作A Dynamic Interface between Vacuoles and Mitochondria in Yeast

细胞亚器文献阅读之酵母液泡与线粒体的动态互作A Dynamic Interface between Vacuoles and Mitochondria in Yeast

本文和前一篇阅读的文献之间的关联，本文发现线粒体依赖于两个接触位点中的一个，ERMES或vCLAMP。前一天的文章也谈到这两个位点。

细胞的生命依赖于脂质和小分子在线粒体和内膜系统之间的连续运输。近年来，内质网-线粒体接触结构（ERMES）被认为是这种转运的一种重要但非必需的接触。利用酵母中的高含量筛选，作者在酵母溶酶体小室（Vam6/Vps39）和线粒体（vCLAMP）之间发现了一个接触位点。vCLAMP富含离子和氨基酸转运体，在内膜系统和线粒体之间的脂质传递中起作用。关键的是，作者发现线粒体依赖于两个接触位点中的一个，ERMES或vCLAMP。缺少一个会导致另一个的膨胀，而消除这两个都是致命的。鉴别vCLAMP增加了我们对细胞器间的互作复杂性的理解能力。

本文作者通过在不同的营养状态下，比如说葡糖糖和正常培养基培养，在三种参与两个膜接触位点的蛋白质的敲除的情况下，通过薄层层析的(TLC)的方法检测线粒体内的磷脂(包括心磷脂CL，磷脂酰乙醇胺，磷脂酰丝氨酸，磷脂酰肌醇)的含量的变化，与此同时，通过H3标记ser来检测ptdser向PtdEtn，进一步向PtdCho转化的过程，即线粒体中合成的磷脂酰乙醇胺和胆碱的情况。这些实验，在单敲除上述三种蛋白的情况下，各种磷脂的减少并不可见。这表明两种膜接触位点ERMES vCLAMP共同调节线粒体内的脂质与ER和Vacuoles囊泡之间的合成和原料的转运，以及不同的细胞器之间功能的协调。

引言部分

Mitochondria generate the majority of cellular energy and house enzymes required for the synthesis, breakdown, and intercon version of various species of amino acids, lipids, iron/sulfur clusters, and other small molecules. Due to their diverse functions and essential roles in cellular metabolism, mitochondria serve as hubs for signaling in events such as growth, differentiation, or cell death. Loss of optimal mitochondrial activity is therefore, not surprisingly, implicated in a growing number of human diseases as well as in aging。

线粒体产生合成、分解和相互转化各种氨基酸、脂质、铁/硫簇和其他小分子所需的大部分细胞能量和酶。由于线粒体在细胞代谢中的不同功能和重要作用，线粒体在诸如生长、分化或细胞死亡等事件中充当信号中枢。因此，毫不奇怪，线粒体最佳活性的丧失与越来越多的人类疾病和衰老有关。

The central tasks of mitochondria in cells necessitate constant communication and transport of small molecules with other organelles. However, mitochondria are not connected to the endomembrane system via the vesicular pathway. Instead, mitochondria have been shown to communicate with the endomembrane system by virtue of a membrane contact site (MCS) where membranes of mitochondria come into close proximity to membranes of the endoplasmic reticulum (ER). This MCS, also termed mitochondria-associated-membranes (Achleitner et al.,1999; Vance, 1990), enables ions and lipids to be rapidly transported in a nonvesicular manner (Elbaz and Schuldiner, 2011; Levine and Loewen, 2006; Tatsuta et al., 2014). Understanding the molecular machineries creating and regulating this MCS has been the arena of intense investigations in the past decade.

细胞内线粒体的中心任务需要小分子与其他细胞器的持续通讯和运输。然而，线粒体并不通过囊泡途径与内膜系统相连。相反，线粒体通过膜接触位点（MCS）与内膜膜系统进行通信，其中线粒体膜接近内质网（ER）的膜。这种MCS也称为线粒体相关膜（Achleitner等人，1999年；Vance，1990年），使离子和脂质以非特异方式快速运输（Elbaz和Schuldiner，2011年；Levine和Loewen，2006年；Tatsuta等人，2014年）。在过去的十年里，了解产生和调节这种MCS的分子机制一直是研究的热点。

In yeast, the molecular identity of the ER-mitochondria tethering complex was recently uncovered and is mediated by a four-protein complex termed the ER-mitochondria encounter structure (ERMES) (Kornmann et al., 2009). One of its hypothesized functions was to enable phospholipid transport (Kopec et al., 2010; Kornmann and Walter, 2010) required for building mitochondrial membranes as well as for the three-step biosynthetic pathway of aminoglycerophospholipids. Therefore, it was of great surprise when the loss of ERMES subunits had very little effect on cellular levels of aminoglycerophospholipids (Kornmann et al., 2009; Nguyen et al., 2012; Voss et al., 2012).
Hence, it became clear that alternate routes of phospholipid transport must exist in the cell, and uncovering them should shed light on novel modes of communication between mitochondria and the endomembrane system. We report here our findings of an MCS between mitochondria and vacuoles (the yeast lysosomal compartment) and its functional significance in lipid tran