Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function.
Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function.
复制标题
Desmin细胞骨架与肌肉线粒体分布和呼吸功能有关。
DOI：
10.1083/jcb.150.6.1283
复制
发表时间：
2000-09-18
影响因子：
7.8
通讯作者：
Capetanaki, Y
中科院分区：
文献类型：
--
作者：
Milner, D J;Mavroidis, M;Weisleder, N;Capetanaki, Y
先前的超微结构研究表明，中间丝(IF)可能与线粒体有关。因此，我们研究了缺乏IF蛋白结蛋白的肌肉中线粒体的分布和功能。骨骼肌组织切片的免疫染色以及线粒体标记酶细胞色素C氧化酶和琥珀酸脱氢酶的组织化学染色显示，在结蛋白缺失的小鼠中，以慢抽动为主的骨骼肌中线粒体的肌膜下异常聚集。对结蛋白缺失的心肌的超微结构观察显示，除了成团外，相当一部分心肌细胞中有广泛的线粒体增殖，特别是在工作超负荷后。这些改变经常与线粒体基质的肿胀和退化有关。线粒体异常可以在其他结构缺陷变得明显之前很早就被发现。为了研究线粒体功能的相关变化，我们分析了ADP刺激的离体肌线粒体的呼吸，以及ADP刺激的原位线粒体呼吸。结蛋白缺失小鼠和野生型小鼠心肌线粒体的体外最大呼吸频率相似。然而，在结蛋白缺失的肌肉中，线粒体的原位呼吸发生了显著的变化。结蛋白缺失的心肌和比目鱼肌ADP刺激的最大耗氧率和ADP的解离常数Km均显著低于对照组。结蛋白缺失的快速抽动腓肠肌的呼吸参数未受影响。此外，在肌酸存在下的呼吸测量表明，在结蛋白缺失的比目鱼肌中，肌酸激酶和腺嘌呤转运体的偶联丢失。这种偶联在结蛋白缺失动物的心肌中不受影响。所有这些研究表明，结蛋白IF在心肌和骨骼肌的线粒体定位和呼吸功能中起着重要作用。
Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (K m) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant role in mitochondrial positioning and respiratory function in cardiac and skeletal muscle.