REGULATION OF ENERGY METABOLISM IN AGING AND DISEASE--CARDIOVASCULAR SYSTEM

该项目研究了老年人和老年人的线粒体功能， 线粒体能量传导减少的病理状态 可能危及组织存活。 今年的实验结果得出 从心力衰竭和心源性心脏病死亡的两个范例 肌细胞(1)我们研究了线粒体内游离Ca 2+的变化， ([Ca2+]m）作为活性较低的丙酮酸的可能机制 脱氢酶，我们在2株先天性 心肌病（B10 14.6和TO.2），并在去年的报告中描述。 用分离的线粒体进行的研究显示， 在肌病和健康菌株中的线粒体膜-即没有 线粒体Ca 2+转运蛋白本身的内在变化。 然而，在离体心肌细胞中原位测定[Ca 2 +]m， 与健康动物相比，肌病动物显示出较低的值， 这是由于电激发时胞质溶胶[Ca 2 +]的瞬变较低。 这些结果为脱氢酶受损提供了可能的机制 在这只动物身上。(2)线粒体功能已经被评估 在分离的心肌细胞中，使用新描述的荧光染料JC- 1，报告线粒体膜电位（Δ psi）。 去- 由于缺氧或呼吸链抑制导致的细胞死亡 允许一些剩余的收缩功能和保存 Δ psi。 糖酵解的额外抑制导致两者的崩溃 参数 显然，糖酵解产生的ATP可以维持Δ psi， 在所采用的实验条件下，通过逆转 线粒体质子转运ATP酶。

This project examines mitochondrial functioning in old age and in pathological states in which decreased energy transduction by mitochondria may compromise tissue survival. Experimental results this year derive from two paradigms relating to heart failure and death of cardiac myocytes. (1) We have investigated a changed intramitochondrial free Ca2+ ([Ca2+]m) as a possible mechanism of the less active pyruvate dehydrogenase which we identified in 2 strains of hamster with an inborn cardiomyopathy (B10 14.6 and TO.2) and described in last year's report. Work with isolated mitochondria showed similar gradients of Ca2+ across the mitochondrial membrane in myopathic and healthy strains - i.e. no intrinsic change in the mitochondrial Ca2+-transport proteins per se. However, measurements of [Ca2+]m in situ in isolated cardiac myocytes from myopathic animals showed lower values compared to healthy animals, thought to be due to lower transients in cytosol [Ca2+] on electrical excitation. These results provide a possible mechanism for the impaired dehydrogenase regulation in this animal. (2) Mitochondrial function has been evaluated in isolated cardiac myocytes using the newly-described fluorescent dye JC- 1, which reports on mitochondrial membrane potential ( delta psi). De- energization of the cells due to anoxia or respiratory chain inhibition allows some remaining measure of contractile function and preservation of delta psi. Additional inhibition of glycolysis leads to collapse of both parameters. Evidently ATP derived from glycolysis can sustain delta psi, under the experimental conditions employed, through a reversal of the mitochondrial protontranslocating ATPase.