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Mitochondrial factor promotes energy production in muscle

COX7RP is required for supercomplex assembly in mitochondria

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University Hospital
2013/08/21

© Kazuhiro Ikeda and Satoshi Inoue. Schematic representation of the functional role of COX7RP in mitochondrial respiration and in muscle and brown adipose tissue. COX7RP promotes the assembly of the I+III+IV supercomplex which is required for full activition of mitochondrial respiration and energy (ATP) synthesis. COX7RP plays important roles in energy production in muscle and heat production in brown adipose tissue. This elucidation of the molecular mechanism of COX7RP action will provide a clue to understanding the mitochondrial contribution to various physiological and pathophysiological states.

Mitochondria are a type of intracellular organelle necessary during aerobic exercise for producing energy through respiration, burning fat and glucose with oxygen. Efficient mitochondrial respiration supplies the energy in muscle to power movement. The process of mitochondrial respiration is driven by 5 enzyme complexes (I, II, II, IV, and V), three of which (I, II, and IV) assemble to form supercomplex. The supercomplex is required to achieve full activation of respiration; however, the mechanism of supercomplex assembly is not clear.

Prof. Satoshi Inoue of the Department of Anti-Aging Medicine in the University of Tokyo Hospital and Dr. Kazuhiro Ikeda of the Research Center for Genomic Medicine in Saitama Medical University have identified COX7RP as a novel factor for promoting supercomplex assembly in mitochondrial respiration. Cox7rp knockout mice exhibit decreased endurance in exercise performance. In contrast, over-expression of COX7RP created marathon runner-type mice with a prolonged endurance time.

COX7RP plays important roles in energy production in muscle and heat production in brown adipose tissue, and as a result may be a target for developing treatments for diseases associated with metabolism and the endocrine system.

This research was supported by Grant-in-Aid for Scientific Research on Innovative Areas and Grants of the Cell Innovation Program from MEXT and was published in Nature Communications on 16 July 2013 (6pm Japan time).

Press release [pdf] (Japanese)

Paper

Ikeda K, Shiba S, Horie-Inoue K, Shimokata K, Inoue K,
“A stabilizing factor for mitochondrial respiratory supercomplex assembly regulates energy metabolism in muscle”,
Nature Communications 4:2147, doi: 10.1038/ncomms3147.
Article link

Links

Graduate School of Medicine

Department of Anti-Aging Medicine, University of Tokyo Hospital (Japanese)

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