Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin
Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin
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DOI：
10.1074/jbc.m116.718510
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发表时间：
2016-07-22
影响因子：
4.8
通讯作者：
Miyoshi, Hideto
中科院分区：
文献类型：
--
作者：
Abe, Masato;Hasegawa, Yui;Miyoshi, Hideto
在线粒体中从头合成心磷脂(CL)后，心磷脂(CL)酰链的重塑是成熟CL的最终分子组成的原因。酿酒酵母经历了他法津介导的CL重塑，其中他法津是一种从磷脂到单聚CL(MLCL)的转酰酶。鉴于成熟CL的酰基组成在不同生物体之间的差异，他法津介导的转酰化的机制仍有待阐明。我们研究了由不同的酰基供体和受体组成的脂质体与纯化的酿酒酵母他法津进行转酰化反应的机理。结果表明，他法津能有效地催化脂膜中高度有序的脂双层结构中的转酰化反应。Tafazzin对磷脂酰胆碱(PC)具有独特的酰基链特异性：亚油酰基(18：2)>；油酰基(18：1)=棕榈油酰基(16：1)>；棕榈酰基(16：0)。在这些反应中，Tafazzin选择性地去除了PC的sn-2酰链，并以相同的速率将其转移到MLCL的sn-1和sn-2位置。我们首次证明了MLCL和DILYSO-CL分别具有作为单聚-PC的酰基供体和PC的酰基受体的固有能力。此外，在我们的实验中，Barth综合征相关的他法津突变体(H77Q)被证明完全缺乏催化活性。目前的结果很难与所谓的热力学重塑假说相一致，该假说假设他法津只在无序的非双层脂类结构域通过不饱和的酰基链与MLCL反应。他法津的酰基专一性可能是决定酿酒酵母成熟线粒体酰基组成的因素之一。
Remodeling of the acyl chains of cardiolipin (CL) is responsible for final molecular composition of mature CL after de novo CL synthesis in mitochondria. Yeast Saccharomyces cerevisiae undergoes tafazzin-mediated CL remodeling, in which tafazzin serves as a transacylase from phospholipids to monolyso-CL (MLCL). In light of the diversity of the acyl compositions of mature CL between different organisms, the mechanism underlying tafazzin-mediated transacylation remains to be elucidated. We investigated the mechanism responsible for transacylation using purified S. cerevisiae tafazzin with liposomes composed of various sets of acyl donors and acceptors. The results revealed that tafazzin efficiently catalyzes transacylation in liposomal membranes with highly ordered lipid bilayer structure. Tafazzin elicited unique acyl chain specificity against phosphatidylcholine (PC) as follows: linoleoyl (18:2) > oleoyl (18:1) = palmitoleoyl (16:1) >> palmitoyl (16:0). In these reactions, tafazzin selectively removed the sn-2 acyl chain of PC and transferred it into the sn-1 and sn-2 positions of MLCL isomers at equivalent rates. We demonstrated for the first time that MLCL and dilyso-CL have inherent abilities to function as an acyl donor to monolyso-PC and acyl acceptor from PC, respectively. Furthermore, a Barth syndrome-associated tafazzin mutant (H77Q) was shown to completely lack the catalytic activity in our assay. It is difficult to reconcile the present results with the so-called thermodynamic remodeling hypothesis, which premises that tafazzin reacylates MLCL by unsaturated acyl chains only in disordered non-bilayer lipid domain. The acyl specificity of tafazzin may be one of the factors that determine the acyl composition of mature CLin S. cerevisiae mitochondria.