CHRONIC REGULATION OF MITOCHONDRIAL CONTENT IN MUSCLE

工作总结：我们正在研究慢性调节 肌肉中线粒体酶活性，以期了解 骨骼肌耐力训练能力下降和虚弱 垂暮之年。我们特别关注协调 线粒体和核基因组在生物发生中的表达 线粒体。我们选择强调细胞色素c氧化酶， 因为它包含每个基因组上编码的亚基。此外，在其职能上 催化电子转移到氧气的最后一步，它施加了 对氧化磷酸化的实质性控制。去年我们展示了 大鼠心肌线粒体细胞色素氧化酶活性降低 作为老化和放射性标记蛋氨酸降低比率的函数 整合到mt-DNA编码的亚基中。今年，我们致力于 建立这一减量机制。我们已经表明，总体上 线粒体基因组的转录，用标记的UTP测量 合并到分离的大鼠心脏线粒体中，随着 老龄(24月龄雄性Wistar大鼠与6月龄雄性Wistar大鼠)。当个人 转录本通过Northern blots进行测定，COX 1的消息是 显著减少，而COX II的消息没有。因为两者都是 编码在mt-DNA上，它被转录成多顺反子信息， 可能涉及消息处理和/或稳定性的其他问题。 细胞色素氧化酶部分核编码亚基的表达 在衰老过程中也会发生变化。因此，我们发现COX V1c蛋白减少 内容。转录因子结合序列的存在 COX V1c基因和MTF-1基因上的NRF-1，这是必不可少的 对于mt-DNA的复制和转录，向我们暗示了许多或 所有这些影响都可以用NRF-1随着年龄的增长而减少来解释 级别。这一点正在研究中。

Summary of work: We are studying the chronic regulation of mitochondrial enzyme activity in muscle, with a view to understanding the weakness and decreased capacity for endurance training of skeletal muscle in old age. We are particularly concerned with mechanisms coordinating the expression of mitochondrial and nuclear genomes in the biogenesis of mitochondria. We have chosen to emphasize the enzyme cytochrome c oxidase, as it contains subunits encoded on each genome. Further, in its function of catalyzing the terminal step of electron transfer to oxygen, it exerts substantial control over oxidative phosphorylation. Last year we showed decreased enzymic activity of cytochrome oxidase in rat heart mitochondria as a function of aging and decreased rates of radiolabelled methionine incorporation into subunits encoded on mt-DNA. This year we have sought to establish the mechanism of this decrement. We have shown that the overall transcription of the mitochondrial genome, measured by labeled UTP incorporation into isolated rat heart mitochondria, is diminished with aging (24 month old male Wistar rat versus 6 month old). When individual transcripts are measured by Northern blots, message for COX 1 was significantly decreased, whereas message for COX II was not. As both are encoded on mt- DNA, which is transcribed to give a polycistronic message, other issues of message processing and/or stabilization may be involved. Expression of some of the nuclear-encoded subunits of cytochrome oxidase is also altered in aging. Thus, we find a decrease in COX V1c protein content. The presence of a binding sequence for the transcription factor NRF-1 on both the COX V1c gene and the gene for MTF-1, which is essential for replication and transcription of mt-DNA, suggests to us that many, or all, of these effects could be explained by a decrease with aging of NRF-1 levels. This is being studied.