Peroxisomal ABC transporters: functions and mechanism.
Peroxisomal ABC transporters: functions and mechanism.
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DOI：
10.1042/bst20150127
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发表时间：
2015-10
影响因子：
3.9
通讯作者：
Theodoulou FL
中科院分区：
文献类型：
--
作者：
Baker A;Carrier DJ;Schaedler T;Waterham HR;van Roermund CW;Theodoulou FL
在所有真核细胞器中，过氧化物体可以说是最具生物化学功能的细胞器。它们的代谢功能在不同的生物体之间、同一生物体的不同组织类型之间、甚至在不同的发育阶段之间或对变化的环境条件的反应中都有所不同。过氧酶体的新功能仍在被发现，其重要性因过氧酶体功能障碍可能出现的严重表型而得到强调。β氧化途径是过氧化物体代谢的中心，但处理的底物非常不同，反映了不同物种的过氧化物体的多样性。β氧化的底物通过D亚家族的转运蛋白进入过氧化体，并被特定的酰辅酶A合成酶激活以进行进一步的代谢。人类有三个过氧化体ABCD家族成员，它们是同源二聚体的一半转运体，具有不同但部分重叠的底物特异性；酿酒酵母有两个异二聚体的一半转运体，植物有一个过氧体ABC转运体，它是一个融合的异二聚体，似乎是非常广泛的β氧化底物进入过氧体的唯一入口点。我们的研究表明，拟南芥Peroxisomal ABC转运蛋白AtABCD1接受酰基CoA底物，在转运之前或运输过程中将其切割，然后被过氧体合成酶重新激活。我们认为，这是一种为这类转运蛋白提供特异性的一般机制，通过这种机制，两亲性化合物可以通过过氧化酶体膜进行移动。
Peroxisomes are arguably the most biochemically versatile of all eukaryotic organelles. Their metabolic functions vary between different organisms, between different tissue types of the same organism and even between different developmental stages or in response to changed environmental conditions. New functions for peroxisomes are still being discovered and their importance is underscored by the severe phenotypes that can arise as a result of peroxisome dysfunction. The β-oxidation pathway is central to peroxisomal metabolism, but the substrates processed are very diverse, reflecting the diversity of peroxisomes across species. Substrates for β-oxidation enter peroxisomes via ATP-binding cassette (ABC) transporters of subfamily D; (ABCD) and are activated by specific acyl CoA synthetases for further metabolism. Humans have three peroxisomal ABCD family members, which are half transporters that homodimerize and have distinct but partially overlapping substrate specificity; Saccharomyces cerevisiae has two half transporters that heterodimerize and plants have a single peroxisomal ABC transporter that is a fused heterodimer and which appears to be the single entry point into peroxisomes for a very wide variety of β-oxidation substrates. Our studies suggest that the Arabidopsis peroxisomal ABC transporter AtABCD1 accepts acyl CoA substrates, cleaves them before or during transport followed by reactivation by peroxisomal synthetases. We propose that this is a general mechanism to provide specificity to this class of transporters and by which amphipathic compounds are moved across peroxisome membranes.