In Cellulo Mapping of Subcellular Localized Bilirubin
In Cellulo Mapping of Subcellular Localized Bilirubin
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DOI：
10.1021/acschembio.6b00017
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发表时间：
2016-08-01
影响因子：
4
通讯作者：
Rhee, Hyun-Woo
中科院分区：
文献类型：
--
作者：
Park, Jong-Seok;Nam, Eunju;Rhee, Hyun-Woo
胆红素（BR）是人体细胞从头合成的代谢物。然而，BR 在人类细胞不同细胞器中的亚细胞定位在很大程度上尚不清楚。在这里，利用 UnaG 作为基因编码的荧光 BR 传感器，我们报告了活细胞的各种细胞器中存在相对 BR 富集和 BR 耗尽的微空间。我们的研究表明，(i) 内质网 (ER) 的细胞质面膜和细胞核是 BR 相对丰富的空间，(ii) 线粒体膜间空间和 ER 腔是 BR 相对贫乏的空间。因此，我们证明了 ER 膜中这种不对称 BR 分布与 BR 代谢途径之间的关系。此外，我们的结果表明其他细胞区室（包括细胞核和线粒体）中可能存在 BR 运输和 BR 调节机制。
Bilirubin (BR) is a de novo synthesized metabolite of human cells. However, subcellular localization of BR in the different organelles of human cells has been largely unknown. Here, utilizing UnaG as a genetically encoded fluorescent BR sensor, we report the existence of relatively BR-enriched and BR-depleted microspaces in various cellular organelles of live cells. Our studies indicate that (i) the cytoplasmic facing membrane of the endoplasmic reticulum (ER) and the nucleus are relatively BR-enriched spaces and (ii) mitochondrial intermembrane space and the ER lumen are relatively BR-depleted spaces. Thus, we demonstrate a relationship between such asymmetrical BR distribution in the ER membrane and the BR metabolic pathway. Furthermore, our results suggest plausible BR-transport and BR-regulating machineries in other cellular compartments, including the nucleus and mitochondria.