Dietzen D J, Davis E J
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202.
Arch Biochem Biophys. 1994 Mar;309(2):341-7. doi: 10.1006/abbi.1994.1122.
Using mitochondria isolated from normal rat liver and AS-30D hepatoma in addition to cholesterol-enriched mitochondria, we have evaluated the ability of membrane cholesterol to induce changes in mitochondrial function, specifically, the preferential export of citrate (i.e., truncation of the Krebs cycle). Two in vitro cholesterol-enrichment procedures failed to produce mitochondria with any physiologically significant increases in free membrane cholesterol. Alternatively, male Wistar rats were maintained on a 2% cholesterol diet to elevate mitochondrial cholesterol. This treatment resulted in liver mitochondria which contained 70% of the cholesterol levels found in AS-30D hepatoma mitochondria, yet only minor metabolic and bioenergetic alterations. Subfractionation of the various mitochondrial preparations revealed that cholesterol was located primarily in outer membranes of both the cholesterol-enriched and AS-30D preparations. We therefore conclude that an increase in membrane cholesterol is not sufficient to induce "truncation" of the citric acid cycle or any other mitochondrial abnormality in tumor cells.
除了使用从正常大鼠肝脏和AS - 30D肝癌中分离出的线粒体以及富含胆固醇的线粒体，我们还评估了膜胆固醇诱导线粒体功能变化的能力，具体而言，就是柠檬酸盐的优先输出（即三羧酸循环的截断）。两种体外胆固醇富集程序均未能产生游离膜胆固醇有任何生理显著增加的线粒体。另外，给雄性Wistar大鼠喂食2%胆固醇饮食以提高线粒体胆固醇水平。这种处理导致肝脏线粒体的胆固醇含量达到AS - 30D肝癌线粒体中胆固醇含量的70%，但仅产生了轻微的代谢和生物能量改变。对各种线粒体制剂进行亚分级分离显示，胆固醇主要位于富含胆固醇制剂和AS - 30D制剂的外膜中。因此，我们得出结论，膜胆固醇的增加不足以诱导肿瘤细胞中柠檬酸循环的“截断”或任何其他线粒体异常。
