Linnane A W, Degli Esposti M, Generowicz M, Luff A R, Nagley P
Centre for Molecular Biology and Medicine, Monash University, Melbourne, Victoria, Australia.
Biochim Biophys Acta. 1995 May 24;1271(1):191-4. doi: 10.1016/0925-4439(95)00027-2.
Overt mitochondrial diseases associated with mitochondrial DNA mutations are characterized by a decline in mitochondrial respiratory function. Similarly, a progressive decline in mitochondrial respiratory function associated with mitochondrial DNA mutations is clearly evidenced in aged human subjects. This communication is concerned with the development of a rat model for the study of bioenergy decline associated with the ageing process and overt mitochondrial diseases. The model involves the treatment of young rats with AZT to induce skeletal and cardiac myopathies. It has shown that there is a decline in soleus muscle function in vivo and that this decline is mirrored in the capacity of heart sub-mitochondrial particles to maintain bioenergy function. Coenzyme Q10 and several analogs were administered with AZT as potential therapeutics for the re-energization of affected tissues. Coenzyme Q10 and especially decyl Q were found to be therapeutically beneficial by both in vivo improvement in soleus muscle function and in vitro cardiac mitochondrial membrane potential capacity. Sub-mitochondrial particles were also prepared from heart mitochondria of young and aged rats. The particles prepared from the aged rats were found to have a decreased ability to maintain membrane potential as compared to those derived from the young rats.
与线粒体DNA突变相关的显性线粒体疾病的特征是线粒体呼吸功能下降。同样，在老年人类受试者中，与线粒体DNA突变相关的线粒体呼吸功能的进行性下降也得到了明确证实。本通讯关注的是一种大鼠模型的建立，用于研究与衰老过程和显性线粒体疾病相关的生物能量下降。该模型包括用叠氮胸苷（AZT）处理幼鼠以诱导骨骼肌和心肌病。结果表明，比目鱼肌在体内的功能下降，并且这种下降反映在心脏亚线粒体颗粒维持生物能量功能的能力上。辅酶Q10和几种类似物与AZT一起作为受影响组织重新获得能量的潜在治疗剂给药。发现辅酶Q10，尤其是癸基Q，通过比目鱼肌功能的体内改善和体外心脏线粒体膜电位能力，在治疗上是有益的。还从年轻和老年大鼠的心脏线粒体中制备了亚线粒体颗粒。与从年轻大鼠获得的颗粒相比，发现从老年大鼠制备的颗粒维持膜电位的能力降低。
