MITOCHONDRIAL FUNCTION AND YEAST METABOLISM REGULATION

我们已经证明了阴离子通过线粒体的运输 膜参与诱导性酒精的调节 酵母脱氢酶(ADH-II)。这一规定反过来又与 通过另一组调节基因调节糖酵解。我们 已经能够排除与 苹果酸-天冬氨酸穿梭，并积累了一些证据表明 ATP-ADP航天飞机没有参与其中。效果最好的航天飞机可能 是二羧酸盐航天器，但其他航天器系统可能比 直接参与，并将在此项目期间进行调查。突变者 提高苹果酸-天冬氨酸航天飞机的效率 从生长的细胞中分离出来，在这种条件下， 将等价物还原到线粒体中是限速的。我们现在是 能够产生既增强又干扰这一点和另一点的突变 航天飞机。这些突变体对ADH调节和遗传学的影响 并将对突变体本身的生理学进行研究。他们是, 据我们所知，在任何影响这些的有机体中首次发现 基本的细胞过程。同时，我们将克隆CCR1，One ADH的两个最重要的调控基因。这个基因也是 参与调节多种糖酵解酶。寻找…… 具有抗诱导物或脱辅酶抑制物特性的小分子将 继续，这些小分子与调节剂的相互作用 将对蛋白质进行研究。这项工作将遵循以下原则 生物化学、生理学、遗传学和分子生物学。增加了…… 我们对酵母中糖酵解的调节的理解将会有 应用于许多其他类型的细胞，因为该过程 对细胞生理学的基本重要性。

We have shown that the transport of anions across the mitochondrial membrane is involved in the regulation of the inducible alcohol dehydrogenase (ADH-II) of yeast. This regulation is in turn tied in with the regulation of glycolysis through another set of regulatory genes. We have been able to rule out the transport mechanisms involved in the malate-aspartate shuttle, and have accumulated some evidence that the ATP-ADP shuttle is not involved. The shuttle with the greatest effect may be the dicarboxylate shuttle, but other shuttle systems may be more directly involved and will be investigated during this project. Mutants enhancing the efficiency of the malate-asparatate shuttle have been isolated from cells grown under conditions in which the transport of reducing equivalents into the mitochondrion are rate-limiting. We are now able to produce mutants that both enhance and interfere with this and other shuttles. The effect of these mutants on ADH regulation and the genetics and physiology of the mutants themselves will be investigated. They are, to our knowledge, the first found in any organism that affect these fundamental cellular processes. At the same time, we will clone CCR1, one of the two most important regulatory genes of ADH. This gene is also involved in the regulation of a number of glycolytic enzymes. A search for small molecules with anti-inducer or apo-repressor properties will continue, and the interaction of these small molecules with regulatory proteins will be investigated. The work will employ the discipline of biochemistry, physiology, genetics and molecular biology. An increase in our understanding of the regulation of glycolysis in yeast will have application to many other types of cells, because the process is of such fundamental importance to cellular physiology.