Juhl Alice Dupont, Wüstner Daniel
Department of Biochemistry and Molecular Biology, PhyLife, Physical Life Sciences, University of Southern Denmark, Odense, Denmark.
Front Cell Dev Biol. 2022 Mar 1;10:834408. doi: 10.3389/fcell.2022.834408. eCollection 2022.
Cholesterol is an essential molecule in cellular membranes, but too much cholesterol can be toxic. Therefore, mammalian cells have developed complex mechanisms to remove excess cholesterol. In this review article, we discuss what is known about such efflux pathways including a discussion of reverse cholesterol transport and formation of high-density lipoprotein, the function of ABC transporters and other sterol efflux proteins, and we highlight their role in human diseases. Attention is paid to the biophysical principles governing efflux of sterols from cells. We also discuss recent evidence for cholesterol efflux by the release of exosomes, microvesicles, and migrasomes. The role of the endo-lysosomal network, lipophagy, and selected lysosomal transporters, such as Niemann Pick type C proteins in cholesterol export from cells is elucidated. Since oxysterols are important regulators of cellular cholesterol efflux, their formation, trafficking, and secretion are described briefly. In addition to discussing results obtained with traditional biochemical methods, focus is on studies that use established and novel bioimaging approaches to obtain insight into cholesterol efflux pathways, including fluorescence and electron microscopy, atomic force microscopy, X-ray tomography as well as mass spectrometry imaging.
胆固醇是细胞膜中的一种必需分子，但过多的胆固醇可能具有毒性。因此，哺乳动物细胞已发展出复杂的机制来清除多余的胆固醇。在这篇综述文章中，我们讨论了关于此类外排途径的已知信息，包括逆向胆固醇转运和高密度脂蛋白的形成、ABC转运蛋白及其他甾醇外排蛋白的功能，并强调了它们在人类疾病中的作用。我们关注了控制甾醇从细胞中外排的生物物理原理。我们还讨论了通过释放外泌体、微囊泡和迁移体实现胆固醇外排的最新证据。阐明了内溶酶体网络、脂质自噬以及选定的溶酶体转运蛋白（如尼曼-皮克C型蛋白）在细胞胆固醇输出中的作用。由于氧化甾醇是细胞胆固醇外排的重要调节因子，因此简要描述了它们的形成、运输和分泌。除了讨论用传统生化方法获得的结果外，重点是利用既定的和新颖的生物成像方法来深入了解胆固醇外排途径的研究，包括荧光和电子显微镜、原子力显微镜、X射线断层扫描以及质谱成像。
