TRANSPORT IN CHOLESTEROL-RICH TUMOR MITOCHONDRIA

肿瘤细胞的富集与肿瘤细胞增殖的关系 线粒体膜与胆固醇在体内和动力学 跨Morris线粒体膜的柠檬酸盐交换转运 肝癌仍然是这些研究的主要目标。 我们 先前提出的富含胆固醇的肿瘤中的“截短”克雷布斯循环 线粒体似乎已经获得了进一步的实验支持。 此外，我们最近在这段拨款期内进行的研究显示， 线粒体膜的大小与 胆固醇富集和柠檬酸盐优先输出的程度 从线粒体基质转移到胞质区室。 因此，我们有 显示正常肝脏胆固醇的外源性富集 线粒体通过我们的“固态”分子转移方法产生的模式 从丙酮酸盐到排泄的柠檬酸盐的碳通量， 模拟了用肿瘤线粒体获得的那些。 我们在一九八四至一九八五年的具体目标之一，是评估 是否 14C-丙酮酸生成的柠檬酸碳优先 新合成的胆固醇中，或者它们是否出现在 主要作为 14CO2当存活的组织切片孵育时， 从Morris肝癌3924 A和正常肝组织中提取的DNA进行了比较， 肝脏 优先将衍生自硼酸盐的碳引入新的 在肿瘤组织中产生的胆固醇将强烈支持我们提出的 肿瘤中代谢模式的改变，包括肿瘤来源的转变， 肿瘤相对于正常组织使用的生物能燃料。 （戊）

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)