TRANSPORT IN CHOLESTEROL-RICH TUMOR MITOCHONDRIA

已有文献记载的肿瘤富集性与 体内含胆固醇的线粒体膜及其动力学 柠檬酸在Morris线粒体膜上的交换转运 肝癌仍然是这些研究的主要目标。我们的 先前提出的富含胆固醇肿瘤的“截短”克雷布斯周期 线粒体似乎得到了进一步的实验支持。 此外，我们在这一赠款期间进行的最新研究表明， 线粒体膜的范围与 富含胆固醇与柠檬酸盐出口优惠程度 从线粒体基质到胞质隔间。因此，我们有 显示外源性胆固醇对正常肝脏的富集性 线粒体通过我们的“固态”分子转移方法产生图案 丙酮酸通过线粒体输出的柠檬酸盐的碳通量 模仿从肿瘤线粒体获得的基因。 我们1984至1985年的具体目标之一是评估 14C-丙酮酸生成的柠檬酸碳是否优先 包含在新合成的胆固醇中，或者它们是否出现在 主要是14CO2，当存活的组织切片孵化时 从Morris肝癌3924A获得的基因与正常对照 肝脏。优先将丙酮酸衍生的碳引入新的 在肿瘤组织中产生的胆固醇将强烈支持我们提出的 肿瘤新陈代谢模式的改变，包括来源的改变 相对于正常组织，肿瘤使用的生物能量燃料。(E)

The relationship between the well-documented enrichment of tumor mitochondrial membranes with cholesterol in vivo and the kinetics of citrate exchange transport across the mitochondrial membranes of Morris hepatomas continue to be the principal objectives of these studies. Our previously proposed "truncated" Krebs cycle in cholesterol-rich tumor mitochondria appears to have obtained further experimental support. Moreover, our recent studies during this grant period have indicated that there is a direct correlation between the extent of mitochondrial membrane enrichment with cholesterol and the extent of preferential citrate export from the mitochondrial matrix to the cytosolic compartment. Thus, we have shown that exogenous enrichment with cholesterol of normal liver mitochondria via our "solid-state" molecule transfer method yields patterns of carbon flux from pyruvate through mitochondrially exported citrate that mimics those obtained with tumor mitochondria. Among our specific objectives for the year 1984 to 1985 is the assessment of whether 14C-pyruvate-generated citrate carbons are preferentially incorporated into newly synthesized cholesterol, or whether they appear predominantly as 14CO2, when incubations of surviving tissue slices obtained from Morris hepatoma 3924A are compared with those from normal liver. Preferential incorporation of pyruvate-derived carbons into newly generated cholesterol in tumor tissue would strongly support our proposed altered pattern of metabolism in tumors, including a shift in the source of bioenergetic fuel used by tumors relative to normal tissue. (E)