小柯机器人

近日，美国宾夕法尼亚大学Zoltan Arany及其研究组发现，线粒体ATP的产生调节内皮脂肪酸的摄取和运输。这一研究成果于2020年6月9日在线发表在《细胞—代谢》上。

研究人员进行了一个小分子筛选，并确定烟酰胺能够抑制内皮脂肪酸（FA）的摄取和运输。结构/活性关系研究表明，烟酰胺通过线粒体解偶联作用。氧化磷酸化和ATP/ADP转移酶的抑制剂也抑制了FA的吸收。通过阻断糖酵解降低总细胞ATP不会降低摄取，这表明专门依赖线粒体ATP。

脂肪酸转运蛋白4（FATP4）通过其ATP依赖性酰基辅酶A合成酶活性促进内皮FA的摄取。共聚焦显微镜显示，FATP4驻留在内质网（ER）中，并且内皮ER与线粒体紧密接触。总之，这些数据表明线粒体ATP的产生而非总ATP的水平通过线粒体/ER微区域中酰基辅酶A的形成来驱动内皮FA的摄取和转运。

据了解，大多数器官都将FA作为关键营养素，但是血液传播的FA如何穿越内皮细胞到达下层组织仍不清楚。

附：英文原文

Title: Local Mitochondrial ATP Production Regulates Endothelial Fatty Acid Uptake and Transport

Author: Ayon Ibrahim, Nora Yucel, Boa Kim, Zoltan Arany

Issue&Volume: 2020-06-09

Abstract: Most organs use fatty acids (FAs) as a key nutrient, but little is known of how blood-borneFAs traverse the endothelium to reach underlying tissues. We conducted a small-moleculescreen and identified niclosamide as a suppressor of endothelial FA uptake and transport.Structure/activity relationship studies demonstrated that niclosamide acts throughmitochondrial uncoupling. Inhibitors of oxidative phosphorylation and the ATP/ADPtranslocase also suppressed FA uptake, pointing principally to ATP production. Decreasingtotal cellular ATP by blocking glycolysis did not decrease uptake, indicating thatspecifically mitochondrial ATP is required. Endothelial FA uptake is promoted by fattyacid transport protein 4 (FATP4) via its ATP-dependent acyl-CoA synthetase activity.Confocal microscopy revealed that FATP4 resides in the endoplasmic reticulum (ER),and that endothelial ER is intimately juxtaposed with mitochondria. Together, thesedata indicate that mitochondrial ATP production, but not total ATP levels, drivesendothelial FA uptake and transport via acyl-CoA formation in mitochondrial/ER microdomains.

DOI: 10.1016/j.cmet.2020.05.018

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30257-6

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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