CHRONIC REGULATION OF MITOCHONDRIAL CONTENT IN MUSCLE

工作总结：我们正在研究慢性病 肌肉中线粒体酶活性的调节 要了解以下方面的弱点和容量下降 老年骨骼肌的耐力训练。我们特别是 关注协调表达的机制 线粒体和核基因组在生物发生中的作用 线粒体。我们选择强调酶 细胞色素C氧化酶，因为它包含编码在每个 基因组。此外，在其催化末端步骤的功能中 电子转移到氧，它在很大程度上控制 氧化磷酸化。去年我们展示了酶的减少 大鼠心脏线粒体细胞色素氧化酶活性的研究 衰老和放射性标记蛋氨酸减少率的作用 整合到mt-DNA编码的亚基中。今年我们有 寻求建立这一减量的机制。我们有 表明线粒体基因组的整体转录， 用标记UTP掺入法测定大鼠离体心 线粒体随着年龄的增长而减少(24个月大的雄性Wistar 老鼠和6个月大的老鼠)。当单个成绩单被测量时 通过Northern杂交，COX-1的信息显著减少， 而给考克斯二世的信息却并非如此。因为两者都在mt-1上编码 转录成多顺反子信息的DNA，其他 可能涉及消息处理和/或稳定性问题。 细胞色素部分核编码亚基的表达 随着年龄的增长，氧化物酶也会发生变化。因此，我们发现考克斯的数量减少了 V1c蛋白含量。结合序列的存在 转录因子NRF-1在COX V1c基因和 MTF-1基因，它是复制和转录所必需的 向我们表明，这些影响中的许多或全部可能 其原因是NRF-1水平随着年龄的增长而降低。这是 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.