Slc25a17 acts as a peroxisomal coenzyme A transporter and regulates multiorgan development in zebrafish
Slc25a17 acts as a peroxisomal coenzyme A transporter and regulates multiorgan development in zebrafish
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DOI：
10.1002/jcp.28954
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发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Choe, Seong-Kyu
中科院分区：
文献类型：
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作者：
Kim, Yong-Il;Nam, In-Koo;Choe, Seong-Kyu
Slc25a17是一种过氧化物酶体溶质载体，但该蛋白在体内的作用尚未得到证实。我们发现，斑马鱼基因组包含两个slc25a17基因，它们的功能是冗余的，但却是相加的。值得注意的是，slc25a17敲低胚胎中的过氧化物酶体功能严重受损，导致脂质组成改变。沿着过氧化物酶体相关表型表达中发现的缺陷，我们强调了鱼鳔的发育也高度依赖于Slc25a17的功能。由于Slc25a17显示出对辅酶A（CoA）的底物特异性，注射CoA而不是NAD（+）拯救了由slc25a17敲低诱导的缺陷性鱼鳔。这些结果表明，Slc25a17作为辅酶A转运蛋白，参与维持功能过氧化物酶体是必不可少的发育过程中的多个器官在斑马鱼胚胎发育。鉴于蛋白质序列的高度同源性，斑马鱼Slc25a17的作用也可能适用于哺乳动物系统。
Slc25a17 is known as a peroxisomal solute carrier, but the in vivo role of the protein has not been demonstrated. We found that the zebrafish genome contains two slc25a17 genes that function redundantly, but additively. Notably, peroxisome function in slc25a17 knockdown embryos is severely compromised, resulting in an altered lipid composition. Along the defects found in peroxisome-associated phenotypic presentations, we highlighted that development of the swim bladder is also highly dependent on Slc25a17 function. As Slc25a17 showed substrate specificity towards coenzyme A (CoA), injecting CoA, but not NAD(+), rescued the defective swim bladder induced by slc25a17 knockdown. These results indicated that Slc25a17 acts as a CoA transporter, involved in the maintenance of functional peroxisomes that are essential for the development of multiple organs during zebrafish embryogenesis. Given high homology in protein sequences, the role of zebrafish Slc25a17 may also be applicable to the mammalian system.