Upregulation of cytochrome c oxidase subunit 6b1 (Cox6b1) and formation of mitochondrial supercomplexes: implication of Cox6b1 in the effect of calorie restriction

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• 作者：Sang-Eun Kim ; Ryoichi Mori ; Toshimitsu Komatsu ; Takuya Chiba ; Hiroko Hayashi…
• 关键词：Calorie restriction ; Cytochrome c oxidase ; Cox6b1 ; Supercomplex
• 刊名：AGE
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：37
• 期：3
• 全文大小：3,277 KB
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• 作者单位：Sang-Eun Kim (1)
  Ryoichi Mori (1)
  Toshimitsu Komatsu (1)
  Takuya Chiba (1) (2)
  Hiroko Hayashi (1)
  Seongjoon Park (1)
  Michiru D. Sugawa (3) (4)
  Norbert A. Dencher (4)
  Isao Shimokawa (1)
  
  1. Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
  2. Biomedical Gerontology Laboratory, Faculty of Human Sciences, and Institute of Applied Brain Sciences, Waseda University, Tokorozawa, 359-1192, Japan
  3. Clinical Neurobiology, Department of Psychiatry, CBF, Charité—Universit?tsmedizin Berlin, D-12203, Berlin, Germany
  4. Physical Biochemistry, Department of Chemistry, Technische Universit?t Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Geriatrics and Gerontology
  Molecular Medicine
  
• 出版者：Springer Netherlands
• ISSN：1574-4647

文摘

Calorie restriction (CR), a non-genetic intervention that promotes longevity in animals, may exert anti-aging effects by modulating mitochondrial function. Based on our prior mitochondrial proteome analysis, we focused on the potential roles of cytochrome c oxidase (Cox or Complex IV) subunit 6b1 on formation of mitochondrial supercomplexes comprised of Complex I, III, and IV. Blue native polyacrylamide gel electrophoresis followed by immunoblotting showed that the amount of Cox6b1 and the proportion of high molecular weight supercomplexes (SCs) comprised of Complexes I, III, and IV were increased in the liver of mice subjected to 30?% CR, compared with the liver of mice fed ad libitum. In in vitro experiments, in Cox6b1-overexpressing NIH3T3 (Cox6b1-3T3) cells, Cox6b1 was increased in the SC, III₂IV₁, and III₂IV₂ complexes and Cox was concomitantly recruited abundantly into the SC, compared with control (Con)-3T3 cells. The proportions of III₂IV₁, and III₂IV₂, relative to IV monomer were also increased in Cox6b1-3T3 cells. Cox6b1-3T3 cells showed increased oxygen consumption rates, Cox activity, and intracellular ATP concentrations, indicating enhanced mitochondrial respiration, compared with Con-3T3 cells. Despite the increased basal level of mitochondrial reactive oxygen species (ROS), cell viability after inducing oxidative stress was greater in Cox6b1-3T3 cells than in Con-3T3 cells, probably because of prompt activation of protective mechanisms, such as nuclear translocation of nuclear factor E2-related factor-2. These in vivo and in vitro studies show that Cox6b1 is involved in regulation of mitochondrial function by promoting the formation of SC, suggesting that Cox6b1 contributes to the anti-aging effects of CR.