CHRONIC REGULATION OF MITOCHONDRIAL CONTENT IN MUSCLE

工作总结： 我们正在研究 线粒体酶活性的肌肉，以期了解 骨骼肌无力和耐力训练能力下降 在老年。我们特别关切的是， 线粒体和核基因组的表达 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，在其功能 催化电子转移到氧气的最后一步， 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速率降低的函数 整合到线粒体DNA上编码的亚基中。今年，我们力求 建立这种递减的机制。我们已经证明， 线粒体基因组的转录，通过标记的UTP测量 掺入到分离的大鼠心脏线粒体中， 老化（24月龄雄性Wistar大鼠与6月龄）。当个别 通过北方印迹测量转录物，对考克斯1的信息是 显著降低，而考克斯II的信息没有。因为两者都是 编码在线粒体DNA上，转录后产生多顺反子信息， 可能涉及消息处理和/或稳定的其它问题。 细胞色素氧化酶部分核编码亚基的表达 也会随着年龄的增长而改变因此，我们发现考克斯V1 c蛋白减少 内容转录因子结合序列的存在 NRF-1对考克斯V1 c基因和MTF-1基因的作用，这是必需的 复制和转录的线粒体DNA，向我们表明，许多，或 所有这些效应都可以通过NRF-1随年龄增长而减少来解释。 程度.这一点正在研究之中。

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.