LYCAT, a homologue of C. elegans acl-8, acl-9, and acl-10, determines the fatty acid composition of phosphatidylinositol in mice
LYCAT, a homologue of C. elegans acl-8, acl-9, and acl-10, determines the fatty acid composition of phosphatidylinositol in mice
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DOI：
10.1194/jlr.m018655
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发表时间：
2012-03-01
影响因子：
6.5
通讯作者：
Arai, Hiroyuki
中科院分区：
文献类型：
--
作者：
Imae, Rieko;Inoue, Takao;Arai, Hiroyuki
哺乳动物磷脂酰肌醇（PI）具有独特的脂肪酸组成，以1-硬脂酰-2-花生四烯醇为主。这种脂肪酸组成是通过连续去酰化和再酰化的脂肪酸重塑形成的。我们最近发现了三种秀丽隐杆线虫酰基转移酶（ACL-8， ACL-9和ACL-10），它们将硬脂酸结合到PI的sn-1位置。哺乳动物LYCAT是与ACL-8、ACL-9和ACL-10最接近的同源物，最初通过体外实验确定为溶心磷脂酰基转移酶，随后报道对各种阴离子溶血磷脂具有酰基转移酶活性。然而，哺乳动物体内LYCAT在磷脂脂肪酸代谢中的作用尚未得到很好的阐明。在这项研究中，我们制造了LYCAT缺陷小鼠，并证明LYCAT在体内决定了PI的脂肪酸组成。lycat缺陷小鼠表面健康，生育能力强。在小鼠中，硬脂酰辅酶a向PI的sn-1位置酰基转移酶活性降低，PI的脂肪酸组成发生变化，但其他主要磷脂的脂肪酸组成未发生变化。此外，小鼠LYCAT的表达挽救了秀丽隐杆线虫acl-8、acl-9、acl-10三重突变体的表型。我们的数据表明LYCAT是PI分子种类的决定因素，其功能在线虫和哺乳动物中是保守的。-今前R.，井上T.，中崎Y.，内田Y.，大叶Y.，河野N.，中西H.，佐佐木T.，三谷S.，新井H.LYCAT是秀丽隐杆线虫acl-8、acl-9和acl-10的同源物，决定小鼠磷脂酰肌醇的脂肪酸组成。[j] .油脂杂志。2012。53: 335 - 347。
Mammalian phosphatidylinositol (PI) has a unique fatty acid composition in that 1-stearoyl-2-arachidonoyl species is predominant. This fatty acid composition is formed through fatty acid remodeling by sequential deacylation and reacylation. We recently identified three Caenorhabditis elegans acyltransferases (ACL-8, ACL-9, and ACL-10) that incorporate stearic acid into the sn-1 position of PI. Mammalian LYCAT, which is the closest homolog of ACL-8, ACL-9, and ACL-10, was originally identified as a lysocardiolipin acyltransferase by an in vitro assay and was subsequently reported to possess acyltransferase activity toward various anionic lysophospholipids. However, the in vivo role of mammalian LYCAT in phospholipid fatty acid metabolism has not been well elucidated. In this study, we generated LYCAT-deficient mice and demonstrated that LYCAT determined the fatty acid composition of PI in vivo. LYCAT-deficient mice were outwardly healthy and fertile. In the mice, stearoyl-CoA acyltransferase activity toward the sn-1 position of PI was reduced, and the fatty acid composition of PI, but not those of other major phospholipids, was altered. Furthermore, expression of mouse LYCAT rescued the phenotype of C. elegans acl-8 acl-9 acl-10 triple mutants. Our data indicate that LYCAT is a determinant of PI molecular species and its function is conserved in C. elegans and mammals.-Imae, R., T. Inoue, Y. Nakasaki, Y. Uchida, Y. Ohba, N. Kono, H. Nakanishi, T. Sasaki, S. Mitani, and H. Arai. LYCAT, a homologue of C. elegans acl-8, acl-9, and acl-10, determines the fatty acid composition of phosphatidylinositol in mice. J. Lipid Res. 2012. 53: 335-347.