Role of Acyl Chain Composition of Phosphatidylcholine in Tafazzin-Mediated Remodeling of Cardiolipin in Liposomes,Biochemistry

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Role of Acyl Chain Composition of Phosphatidylcholine in Tafazzin-Mediated Remodeling of Cardiolipin in Liposomes
Biochemistry ( IF 2.9 ) Pub Date : 2017-11-09 00:00:00 , DOI: 10.1021/acs.biochem.7b00941
Masato Abe ₁ , Yoshiki Sawada ₁ , Shinpei Uno ₁ , Shuhei Chigasaki ₁ , Masahide Oku ₁ , Yasuyoshi Sakai ₁ , Hideto Miyoshi ₁

Affiliation

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.

中文翻译：

磷脂酰胆碱的酰基链组成在Tafazzin介导的脂质体心磷脂重塑中的作用

通过转酰基酶他扎锌对心磷脂（CL）物种的酰基链组成进行重塑是维持最佳线粒体功能的重要过程。关于tafazzin介导的人工脂质膜中从磷脂酰胆碱（PC）到单溶酶（MLCL）的转酰基作用的机理研究的结果是有争议的。本研究通过检查构成二棕榈油酰基（16：1）PC优于二棕榈油酰基（16：0）的优异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tafazzin介导的CL重塑中的作用。个人电脑。为此，我们合成了二棕榈油酰PC的系统衍生物。例如顺式的位置双键从Δ9位移向酰基链的任一端（Δ5-或Δ13位），sn -1或sn -2位置或两者的顺式双键转变为反式，棕榈油酰基和棕榈酰基在sn -1和sn -2位置交换，保持了相似的PC流动性。分析了tafazzin介导的脂质体膜中从这些PC到sn -2'-MLCL（18：1-18：1/18：1-OH）的酰基转移反应，发现tafazzin严格区分了PC酰基链的分子构型，包括它们的甘油位置（sn -1或sn-2）; 但是，PC流动性对反应的影响可能不会被忽略。基于本文描述的发现，我们讨论所谓的热力学重塑假说的相关性，该假说假设没有他发嗪的酰基选择性。

更新日期：2017-11-09

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