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Myoglobin and the regulation of mitochondrial respiratory chain complex IV
Author(s) -
Yamada Tatsuya,
Takakura Hisashi,
Jue Thomas,
Hashimoto Takeshi,
Ishizawa Rie,
Furuichi Yasuro,
Kato Yukio,
Iwanaka Nobumasa,
Masuda Kazumi
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270824
Subject(s) - mitochondrion , myoglobin , biology , cytochrome c oxidase , microbiology and biotechnology , skeletal muscle , myogenesis , mitochondrial dna , respiratory chain , mitochondrial myopathy , myocyte , oxidative phosphorylation , nrf1 , alternative oxidase , respiration , coenzyme q – cytochrome c reductase , biochemistry , mitochondrial biogenesis , cytochrome c , anatomy , gene
Key points Mitochondrial respiration is regulated by multiple elaborate mechanisms. It has been shown that muscle specific O 2 binding protein, Myoglobin (Mb), is localized in mitochondria and interacts with respiratory chain complex IV, suggesting that Mb could be a factor that regulates mitochondrial respiration. Here, we demonstrate that muscle mitochondrial respiration is improved by Mb overexpression via up‐regulation of complex IV activity in cultured myoblasts; in contrast, suppression of Mb expression induces a decrease in complex IV activity and mitochondrial respiration compared with the overexpression model. The present data are the first to show the biological significance of mitochondrial Mb as a potential modulator of mitochondrial respiratory capacity.Abstract 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.