MFE1, a Member of the Peroxisomal Hydroxyacyl Coenzyme A Dehydrogenase Family, Affects Fatty Acid Metabolism Necessary for Morphogenesis in Dictyostelium spp
MFE1, a Member of the Peroxisomal Hydroxyacyl Coenzyme A Dehydrogenase Family, Affects Fatty Acid Metabolism Necessary for Morphogenesis in Dictyostelium spp
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DOI：
10.1128/ec.2.3.638-645.2003
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发表时间：
2003-06
期刊：
影响因子：
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通讯作者：
Satomi Matsuoka;Tamao Saito;H. Kuwayama;N. Morita;H. Ochiai;M. Maeda
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作者：
Satomi Matsuoka;Tamao Saito;H. Kuwayama;N. Morita;H. Ochiai;M. Maeda
摘要 长链脂肪酸和支链脂肪酸的 β-氧化是在哺乳动物过氧化物酶体中通过多功能酶 (MFE) 或 d-双功能蛋白进行的，具有羟酰辅酶 A (CoA) 脱氢酶、烯酰辅酶 A 水合酶和类固醇载体蛋白 SCP2 的单独结构域。我们发现盘基网柄菌有一个基因 mfeA，编码与羟酰辅酶 A 脱氢酶和 SCP2 结构域同源的 MFE1。一个单独的基因 mfeB 编码与烯酰辅酶 A 水合酶结构域同源的 MFE2。当以细菌为食生长时，mfeA 被破坏的盘基网柄菌细胞会积累过量的环丙烷脂肪酸，并且无法在早期聚集后发育。然而，同质生长的突变细胞发育成由孢子和茎细胞组成的正常子实体。全细胞脂质成分的比较分析表明，细菌生长的突变细胞积累了环丙烷脂肪酸，这些脂肪酸在整个发育阶段都保留下来。在野生型细胞或无菌生长的突变细胞中没有检测到这种持续积累。含有丰富环丙烷脂肪酸的细菌磷脂酰乙醇胺甚至能抑制无菌生长的突变细胞的发育，而二棕榈酰磷脂酰乙醇胺则不会。这些结果表明，MFE1 可以保护细胞免受饮食中有害外源脂肪酸增加的影响，并优化细胞脂质组成以促进正常发育。因此，我们认为这种酶在盘基网柄菌细胞形成孢子以使其在自然界中有效传播的生存策略中发挥着不可替代的作用。
ABSTRACT β-Oxidation of long-chain fatty acids and branched-chain fatty acids is carried out in mammalian peroxisomes by a multifunctional enzyme (MFE) or d-bifunctional protein, with separate domains for hydroxyacyl coenzyme A (CoA) dehydrogenase, enoyl-CoA hydratase, and steroid carrier protein SCP2. We have found that Dictyostelium has a gene, mfeA, encoding MFE1 with homology to the hydroxyacyl-CoA dehydrogenase and SCP2 domains. A separate gene, mfeB, encodes MFE2 with homology to the enoyl-CoA hydratase domain. When grown on a diet of bacteria, Dictyostelium cells in which mfeA is disrupted accumulate excess cyclopropane fatty acids and are unable to develop beyond early aggregation. Axenically grown mutant cells, however, developed into normal fruiting bodies composed of spores and stalk cells. Comparative analysis of whole-cell lipid compositions revealed that bacterially grown mutant cells accumulated cyclopropane fatty acids that remained throughout the developmental stages. Such a persistent accumulation was not detected in wild-type cells or axenically grown mutant cells. Bacterial phosphatidylethanolamine that contains abundant cyclopropane fatty acids inhibited the development of even axenically grown mutant cells, while dipalmitoyl phosphatidylethanolamine did not. These results suggest that MFE1 protects the cells from the increase of the harmful xenobiotic fatty acids incorporated from their diets and optimizes cellular lipid composition for proper development. Hence, we propose that this enzyme plays an irreplaceable role in the survival strategy of Dictyostelium cells to form spores for their efficient dispersal in nature.