Abe Masato, Sawada Yoshiki, Uno Shinpei, Chigasaki Shuhei, Oku Masahide, Sakai Yasuyoshi, Miyoshi Hideto
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University , Sakyo-ku, Kyoto 606-8502, Japan.
Biochemistry. 2017 Nov 28;56(47):6268-6280. doi: 10.1021/acs.biochem.7b00941. Epub 2017 Nov 9.
Remodeling of the acyl chain compositions of cardiolipin (CL) species by the transacylase tafazzin is an important process for maintaining optimal mitochondrial functions. The results of mechanistic studies on the tafazzin-mediated transacylation from phosphatidylcholine (PC) to monolyso-CL (MLCL) in artificial lipid membranes are controversial. The present study investigated the role of the acyl chain composition of PC in the Saccharomyces cerevisiae tafazzin-mediated remodeling of CL by examining the structural factors responsible for the superior acyl donor ability of dipalmitoleoyl (16:1) PC over dipalmitoyl (16:0) PC. To this end, we synthesized systematic derivatives of dipalmitoleoyl PC; for example, the location of the cis double bond was migrated from the Δ9-position toward either end of the acyl chains (the Δ5- or Δ13-position), the cis double bond in the sn-1 or sn-2 position or both, was changed to a trans form, and palmitoleoyl and palmitoyl groups were exchanged in the sn-1 and sn-2 positions, maintaining similar PC fluidities. Analyses of the tafazzin-mediated transacylation from these PCs to sn-2'-MLCL(18:1-18:1/18:1-OH) in the liposomal membrane revealed that tafazzin strictly discriminates the molecular configuration of the acyl chains of PCs, including their glycerol positions (sn-1 or sn-2); however, the effects of PC fluidity on the reaction may not be neglected. On the basis of the findings described herein, we discuss the relevance of the so-called thermodynamic remodeling hypothesis that presumes no acyl selectivity of tafazzin.
通过转酰基酶塔法兹蛋白重塑心磷脂（CL）物种的酰基链组成是维持线粒体最佳功能的重要过程。关于塔法兹蛋白介导的磷脂酰胆碱（PC）向人工脂质膜中的单溶血-CL（MLCL）转酰基化的机制研究结果存在争议。本研究通过检查导致二棕榈油酰基（16:1）PC比二棕榈酰基（16:0）PC具有更高酰基供体能力的结构因素，研究了PC的酰基链组成在酿酒酵母塔法兹蛋白介导的CL重塑中的作用。为此，我们合成了二棕榈油酰基PC的系统衍生物；例如，顺式双键的位置从Δ9位向酰基链的任一端（Δ5或Δ13位）迁移，sn-1或sn-2位或两者中的顺式双键变为反式形式，并且棕榈油酰基和棕榈酰基在sn-1和sn-2位进行交换，同时保持相似的PC流动性。对这些PC在脂质体膜中向sn-2'-MLCL(18:1-18:1/18:1-OH)的塔法兹蛋白介导的转酰基化分析表明，塔法兹蛋白严格区分PC酰基链的分子构型，包括其甘油位置（sn-1或sn-2）；然而，PC流动性对反应的影响也不可忽视。基于本文所述的研究结果，我们讨论了假定塔法兹蛋白无酰基选择性的所谓热力学重塑假说的相关性。
