Deadlier than the malate
Deadlier than the malate
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DOI：
10.1038/s41422-018-0042-6
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发表时间：
2018-05
期刊：
影响因子：
44.1
通讯作者：
P. Ding;Hailong Guo;Jonathan D. G. Jones
中科院分区：
文献类型：
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作者：
P. Ding;Hailong Guo;Jonathan D. G. Jones
苹果酸（Malate）是由所有生物体。在植物中，苹果酸有助于酸味水果的愉快味道。然而，在最近发表在Cell Research上的一篇论文中，Zhao等人1报道了苹果酸在植物和动物细胞死亡中的新作用。这是第一次报道，苹果酸从叶绿体（植物特有的光合细胞器）转移到线粒体可以导致细胞在连续光照下死亡。植物和动物的程序性细胞死亡（PCD）通过消除不需要的细胞和响应环境刺激在发育中起着重要作用。细胞内活性氧（ROS）水平的过度升高可导致脂质、蛋白质和DNA的损伤，称为氧化应激，并诱导植物和动物的PCD。然而，ROS也可以作为信号分子。ROS不仅可以通过细胞表面NADPH氧化酶产生，而且可以在线粒体（植物和动物）或叶绿体（植物）中产生。[2]同一研究小组先前报道了MOD 1（镶嵌死亡1）（一种位于叶绿体中的脂肪酸合成酶（FAS））的功能丧失，导致烯酰-ACP还原酶活性降低。3他们进一步观察到ROS在FAS缺陷突变体mod 1中的积累，这导致细胞过早死亡和形态改变，如拟南芥的侏儒症。4.为了确定由MOD 1功能障碍触发的调节细胞死亡的组分，作者筛选了MOD 1抑制剂，并在编码线粒体电子传递链（mETC）复合物I组分的基因中发现了突变。4这些观察结果表明，信号可能从叶绿体传递到线粒体。为了验证这一假设，Zhao等人筛选了其他具有完整mETC复合物I活性的mod 1抑制子。1他们报告了编码质体烟酰胺腺嘌呤二核苷酸（NAD）依赖性苹果酸脱氢酶（plNAD-MDH）、叶绿体二羧酸转运蛋白1（DiT 1）和线粒体苹果酸脱氢酶1（mMDH 1）的基因的新突变。这些蛋白质都是植物中苹果酸/草酰乙酸（OAA）穿梭的关键组分。Zhao等人还证实，mod 1突变体中脂肪酸合成的受损可诱导叶绿体中苹果酸的积累，随后导致叶绿体和线粒体中的氧化应激。1作者进一步证实了plNAD-MDH蛋白定位于叶绿体中，与MOD 1相同。DiT 1位于叶绿体被膜中，其推定功能之一是将苹果酸从叶绿体输出到细胞质，而mMDH 1定位于线粒体。在mod 1突变体中，pINAD-MDH在叶绿体中将OAA还原为苹果酸，而mMDH 1在线粒体中将苹果酸氧化为OAA。这些
Malate (malic acid) is made by all organisms. In plants, malate contributes to the pleasant taste in sour fruits. However, in a recent paper published in Cell Research, Zhao et al. 1 reported a novel role of malate in cell death of both plants and animals. It is the first report that the malate transfer from chloroplasts (the plant-specific photosynthetic organelle) to mitochondria can lead to cell death under continuous light. Programmed cell death (PCD) in plants and animals plays an important role in development by eliminating unwanted cells and in response to environmental stimuli. Excessive elevation of intracellular levels of reactive oxygen species (ROS) can cause damage to lipids, proteins and DNA, known as oxidative stress, and induces PCD in both plants and animals. However, ROS can also serve as signaling molecules. ROS can be generated not only via cell surface NADPH oxidases but also in mitochondria (in both plants and animals) or chloroplasts (in plants). 2 The same group reported previously that loss of function of MOD1 (mosaic death 1), a chloroplast-localized component of fatty acid synthase (FAS), leads to decreased enoyl-ACP reductase activity. 3 They further observed ROS accumulation in the FAS-deficient mutant mod1, which leads to premature cell death and altered morphology such as dwarfism in Arabidopsis. 4 To identify the components regulating cell death triggered by the dysfunction of MOD1, the authors screened for mod1 suppressors and found mutations in genes encoding components of the mitochondrial electron transport chain (mETC) complex I. 4 These observations suggested that a signal might be transduced from chloroplasts to mitochondria.To test this hypothesis, Zhao et al. screened for additional mod1 suppressors with intact mETC complex I activities. 1 They reported new mutations in genes that encode a plastidial nicotinamide adenine dinucleotide (NAD)-dependent malate dehydrogenase (plNAD-MDH), a chloroplastic dicarboxylate transporter 1 (DiT1) and a mitochondrial malate dehydrogenase 1 (mMDH1). These proteins are all key components of the malate/oxaloacetate (OAA) shuttle in plants. Zhao et al. also confirmed that the impairment of fatty acid synthesis in mod1 mutant can induce malate accumulation in chloroplasts, which subsequently causes oxidative stress in both chloroplasts and mitochondria. 1 The authors then verified that plNAD-MDH protein is localized in chloroplasts, the same as MOD1. DiT1 resides in the chloroplast envelope and one of its putative functions is to export malate from chloroplasts to the cytosol, whereas mMDH1 localizes to mitochondria. In mod1 mutant, pINAD-MDH reduces OAA to malate in chloroplasts, and mMDH1 oxidizes malate to OAA in mitochondria. These