摘要
The scavenger receptor class B type 1 (SR-B1) facilitates uptake of cholesterol and carotenoids into the plasma membrane (PM) of mammalian cells. Downstream of SR-B1, ASTER-B protein mediates the nonvesicular transport of cholesterol to mitochondria for steroidogenesis. Mitochondria also are the place for the processing of carotenoids into diapocarotenoids by β-carotene oxygenase-2. However, the role of these lipid transport proteins in carotenoid metabolism has not yet been established. Herein, we showed that the recombinant StART-like lipid-binding domain of ASTER-A and B preferentially binds oxygenated carotenoids such as zeaxanthin. We established a novel carotenoid uptake assay and demonstrated that ASTER-B expressing A549 cells transport zeaxanthin to mitochondria. In contrast, the pure hydrocarbon β-carotene is not transported to the organelles, consistent with its metabolic processing to vitamin A in the cytosol by β-carotene oxygenase-1. Depletion of the PM from cholesterol by methyl-β-cyclodextrin treatment enhanced zeaxanthin but not β-carotene transport to mitochondria. Loss-of-function assays by siRNA in A549 cells and the absence of zeaxanthin accumulation in mitochondria of ARPE19 cells confirmed the pivotal role of ASTER-B in this process. Together, our study in human cell lines established ASTER-B protein as key player in nonvesicular transport of zeaxanthin to mitochondria and elucidated the molecular basis of compartmentalization of the metabolism of nonprovitamin A and provitamin A carotenoids in mammalian cells.
摘要译文
清道夫受体B类1（SR-B1）促进了胆固醇和类胡萝卜素摄取哺乳动物细胞的质膜（PM）。SR-B1的下游，Aster-B蛋白介导胆固醇向线粒体的无抗转运以进行类固醇生成。线粒体也是将类胡萝卜素通过β-胡萝卜素氧酶-2加工成乳突核的地方。但是，这些脂质转运蛋白在类胡萝卜素代谢中的作用尚未确定。在本文中，我们表明，Aster-A和B的重组样启动样脂质结合结构域优先结合氧气的类胡萝卜素，例如Zeaxanthin。我们建立了一种新型的类胡萝卜素摄取测定法，并证明了表达A549细胞的Aster-B将Zeaxanthin转运为线粒体。相比之下，纯碳氢化合物β-胡萝卜素未转移到细胞器中，与β-羟胡托烯氧酶-1在胞质醇中的代谢加工一致。通过甲基-β-环糊精的胆固醇从胆固醇中耗尽可增强Zeaxanthin，而不是β-胡萝卜素转运到线粒体。siRNA在A549细胞中的功能丧失测定，以及在ARPE19细胞线粒体中缺乏Zeaxanthin积累，证实了Aster-B在此过程中的关键作用。我们在人类细胞系中的研究共同确立了紫杉素到线粒体的非氧化转运的关键参与者，并阐明了乳腺细胞中非促毒素A代谢的分子基础，并阐明了非促毒素A和Provitamin a carotenoids的分子基础。
Sepalika Bandara; Jean Moon; Srinivasagan Ramkumar; Johannes von Lintig. ASTER-B regulates mitochondrial carotenoid transport and homeostasis[J]. Journal of Lipid Research, 2023,64(5)