AAE13 encodes a dual-localized malonyl-CoA synthetase that is crucial for mitochondrial fatty acid biosynthesis
AAE13 encodes a dual-localized malonyl-CoA synthetase that is crucial for mitochondrial fatty acid biosynthesis
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DOI：
10.1111/tpj.13130
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发表时间：
2016-03-01
期刊：
影响因子：
7.2
通讯作者：
Nikolau, Basil J.
中科院分区：
文献类型：
--
作者：
Guan, Xin;Nikolau, Basil J.
丙二酰辅酶A是许多代谢过程中的关键中间体，与其在酰化和缩合反应中作为底物的作用相关。这些类型的反应发生在质体、细胞质和线粒体中，尽管乙酰辅酶A的羧化是产生不同质体和细胞质池的已知机制，但线粒体丙二酰辅酶A池的代谢起源仍不清楚。在这项研究中，我们表明，丙二酰辅酶A合成酶编码的拟南芥AAE 13（AT 3G 16170）基因定位在细胞质和线粒体。这些同种型从两种类型的转录物翻译而来，一种含有和一种不含有靶向尿道的前序列。然而，由于存在由胞质乙酰辅酶A羧化酶提供的冗余丙二酰辅酶A生成系统，胞质AAE 13蛋白不是必需的，线粒体AAE 13蛋白对于植物生长是必需的。只有当线粒体前序列存在于异位表达的AAE 13蛋白中时，AAE 13 -1突变体的表型才被转基因逆转。aae 13 -1突变体表现出与线粒体脂肪酸合成酶系统缺陷相关的典型代谢表型，即光呼吸酶甘氨酸脱羧酶H亚基的脂酰化减少，甘氨酸和乙醇酸积累增加，蔗糖水平降低。当aae 13 -1突变体在非光呼吸条件下生长时，大多数这些代谢改变和相关的形态学改变被逆转（即1%CO2气氛），这表明它们是由于不能从脂肪合成的脂肪酸产生硫辛酸而导致的光呼吸不足的结果。辅酶A是质体、细胞质和线粒体中许多代谢过程的关键中间体，但线粒体丙二酰辅酶A库的起源尚不清楚。在这里，我们表明，线粒体脂肪酸合成酶系统使用的丙二酰辅酶A产生的一个naturally位于丙二酰辅酶A合成酶。
Malonyl-CoA is a key intermediate in a number of metabolic processes associated with its role as a substrate in acylation and condensation reactions. These types of reactions occur in plastids, the cytosol and mitochondria, and although carboxylation of acetyl-CoA is the known mechanism for generating the distinct plastidial and cytosolic pools, the metabolic origin of the mitochondrial malonyl-CoA pool is still unclear. In this study we demonstrate that malonyl-CoA synthetase encoded by the Arabidopsis AAE13 (AT3G16170) gene is localized in both the cytosol and the mitochondria. These isoforms are translated from two types of transcripts, one that contains and one that does not contain a mitochondrial-targeting pre-sequence. Whereas the cytosolic AAE13 protein is not essential, due to the presence of a redundant malonyl-CoA generating system provided by a cytosolic acetyl-CoA carboxylase, the mitochondrial AAE13 protein is essential for plant growth. Phenotypes of the aae13-1 mutant are transgenically reversed only if the mitochondrial pre-sequence is present in the ectopically expressed AAE13 proteins. The aae13-1 mutant exhibits typical metabolic phenotypes associated with a deficiency in the mitochondrial fatty acid synthase system, namely depleted lipoylation of the H subunit of the photorespiratory enzyme glycine decarboxylase, increased accumulation of glycine and glycolate and reduced levels of sucrose. Most of these metabolic alterations, and associated morphological changes, are reversed when the aae13-1 mutant is grown in a non-photorespiratory condition (i.e. a 1% CO2 atmosphere), demonstrating that they are a consequence of the deficiency in photorespiration due to the inability to generate lipoic acid from mitochondrially synthesized fatty acids.Significance Statement Malonyl-CoA is a key intermediate in a number of metabolic processes that occur in plastids, the cytosol and mitochondria, but the origin of the mitochondrial malonyl-CoA pool was unclear. Here we show that the mitochondrial fatty acid synthase system uses malonyl-CoA generated by a mitochondrially located malonyl-CoA synthetase.