Myoglobin and the regulation of mitochondrial respiratory chain complex IV
Myoglobin and the regulation of mitochondrial respiratory chain complex IV
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DOI：
10.1113/jp270824
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发表时间：
2016-01-15
影响因子：
5.5
通讯作者：
Masuda, Kazumi
中科院分区：
文献类型：
--
作者：
Yamada, Tatsuya;Takakura, Hisashi;Masuda, Kazumi
线粒体是新陈代谢的重要细胞器，其呼吸能力是调节能量消耗的主要因素。细胞色素 C 氧化酶复合物 IV 的缺乏会减少线粒体中的 O-2，与多种疾病有关，例如线粒体肌病。此外，骨骼肌组织中的线粒体呼吸往往容易受到复杂 IV 活性的影响。最近，我们发现肌肉特异性蛋白肌红蛋白 (Mb) 与复合物 IV 相互作用。线粒体 Mb 的确切作用仍不清楚。在这里，我们证明 Mb 可以促进骨骼肌中的线粒体呼吸能力。尽管 Mb 过表达肌管中的线粒体 DNA 拷贝数没有改变，但这些肌管中的 O-2 消耗量高于模拟细胞（模拟与 Mb-Flag::GFP：状态 4，1.00 +/- 0.09 与 1.77 +/- 0.34；状态 3，1.00 +/- 0.29；模拟：1.60 +/- 0.53；复合体2-3-4：1.00 +/- 0.30 对比 1.50 +/- 0.44；复合物 IV：1.00 +/- 0.14 对比 1.87 +/- 0.27）。呼吸能力的改善可能是由于呼吸复合物酶活性的激活。此外，在短暂过表达 Mb 的成肌细胞中，线粒体呼吸被上调。复合体IV活性仅在Mb过表达的成肌细胞中被激活，并且在通过Mb-siRNA转染抑制Mb表达的成肌细胞中复合体IV活性降低（转染Mb载体与Mb载体、转染对照siRNA与Mb载体、转染Mb siRNA：0.15 vs. 0.15 vs. 0.06）。因此，Mb增强复合物IV的酶活性，改善线粒体呼吸能力，并在骨骼肌代谢中发挥关键作用。
Mitochondria are important organelles for metabolism, and their respiratory capacity is a primary factor in the regulation of energy expenditure. Deficiencies of cytochrome c oxidase complex IV, which reduces O-2 in mitochondria, are linked to several diseases, such as mitochondrial myopathy. Moreover, mitochondrial respiration in skeletal muscle tissue tends to be susceptible to complex IV activity. Recently, we showed that the muscle-specific protein myoglobin (Mb) interacts with complex IV. The precise roles of mitochondrial Mb remain unclear. Here, we demonstrate that Mb facilitates mitochondrial respiratory capacity in skeletal muscles. Although mitochondrial DNA copy numbers were not altered in Mb-overexpressing myotubes, O-2 consumption was greater in these myotubes than that in mock cells (Mock vs. Mb-Flag::GFP: state 4, 1.00 +/- 0.09 vs. 1.77 +/- 0.34; state 3, 1.00 +/- 0.29; Mock: 1.60 +/- 0.53; complex 2-3-4: 1.00 +/- 0.30 vs. 1.50 +/- 0.44; complex IV: 1.00 +/- 0.14 vs. 1.87 +/- 0.27). This improvement in respiratory capacity could be because of the activation of enzymatic activity of respiratory complexes. Moreover, mitochondrial respiration was up-regulated in myoblasts transiently overexpressing Mb; complex IV activity was solely activated in Mb-overexpressing myoblasts, and complex IV activity was decreased in the myoblasts in which Mb expression was suppressed by Mb-siRNA transfection (Mb vector transfected vs. Mb vector, control siRNA transfected vs. Mb vector, Mb siRNA transfected: 0.15 vs. 0.15 vs. 0.06). Therefore, Mb enhances the enzymatic activity of complex IV to ameliorate mitochondrial respiratory capacity, and could play a pivotal role in skeletal muscle metabolism.