Department of Biochemistry and Biocenter Oulu, University of Oulu, P.O.B. 3000, FI-90014 Oulu, Finland.
Prog Lipid Res. 2010 Jan;49(1):27-45. doi: 10.1016/j.plipres.2009.08.001. Epub 2009 Aug 15.
The highly conserved fatty acid de novo synthesis pathway in mitochondria proceeds in an acyl carrier protein-dependent manner through a discrete set of enzymes. Saccharomyces cerevisiae has served as a model for studies of mitochondrial fatty acid synthesis type II (FAS II) and as a template for identification of mammalian components. Inactivation of mitochondrial FAS II in yeast results in respiratory deficiency and loss of cytochromes. The pathway produces the octanoyl-ACP substrate for lipoic acid synthesis, but several pieces of evidence indicate that it is capable of the generation of longer fatty acids. A number of structures of mitochondrial FAS II enzymes have been published in the past few years, allowing for a comparison with their prokaryotic counterparts, several of which have been described as promising targets for antibiotics. Recently, novel links between mitochondrial FAS and RNA processing in yeast and vertebrates have been reported. In S. cerevisiae, deficiency in mitochondrial FAS results in failure of maturation of mitochondrial RNAse P, while, in mammals, mitochondrial 3-hydroxyacyl thioester dehydratase and the RPP14 subunit of RNase P are encoded by the same bicistronic transcript. The first publications linking mitochondrial FAS II to disease states in mammals are emerging.
线粒体中高度保守的脂肪酸从头合成途径通过一组离散的酶以酰基辅酶 A 蛋白依赖性的方式进行。酿酒酵母已被用作线粒体脂肪酸合成 II 型 (FAS II) 研究的模型，并作为鉴定哺乳动物成分的模板。酵母中线粒体 FAS II 的失活导致呼吸缺陷和细胞色素丧失。该途径产生用于硫辛酸合成的辛酰基-ACP 底物，但有几项证据表明它能够生成更长的脂肪酸。过去几年已经发表了许多线粒体 FAS II 酶的结构，允许与它们的原核对应物进行比较，其中一些已被描述为有希望的抗生素靶标。最近，在酵母和脊椎动物中线粒体 FAS 与 RNA 加工之间的新联系已经被报道。在酿酒酵母中，线粒体 FAS 的缺乏导致线粒体 RNAse P 的成熟失败，而在哺乳动物中，线粒体 3-羟基酰基辅酶脱水酶和 RNAse P 的 RPP14 亚基由同一双顺反子转录本编码。将线粒体 FAS II 与哺乳动物疾病状态联系起来的第一批出版物正在出现。
