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Control of Human Energy Expenditure by Cytochrome C Oxidase Subunit IV-2.
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.ORCID iD: 0000-0002-4030-5437
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2016 (English)In: American Journal of Physiology - Cell Physiology, ISSN 0363-6143, E-ISSN 1522-1563, Vol. 311, no 3, C452-C461 p.Article in journal (Refereed) Published
Abstract [en]

Resting metabolic rate (RMR) in human shows pronounced individual variations, but the underlying molecular mechanism remains elusive. Cytochrome C oxidase (COX) plays a key role in control of metabolic rate and recent studies of the subunit 4 isoform 2 (COX IV-2) indicate involvement in the cellular response to hypoxia and oxidative stress. We evaluated whether the COX subunit IV isoform composition may explain the pronounced individual variations in resting metabolic rate (RMR). RMR was determined in healthy humans by indirect calorimetry and correlated to levels of COX IV-2 and COX IV-1 in Vastus Lateralis. Over expression and knock down of the COX IV isoforms were performed in primary myotubes followed by evaluation of the cell respiration and production of reactive oxygen species. Here we show that COX IV-2 protein is constitutively expressed in human skeletal muscle and strongly correlated to RMR. Primary human myotubes overexpressing COX IV-2 displayed markedly (>60%) lower respiration, reduced (>50%) cellular H2O2 production, higher resistance towards both oxidative stress and severe hypoxia compared to control cells. These results suggest an important role of isoform COX IV-2 in the control of energy expenditure, hypoxic tolerance and mitochondrial ROS homeostasis in humans.

Place, publisher, year, edition, pages
2016. Vol. 311, no 3, C452-C461 p.
National Category
Physiology
Research subject
Medicine/Technology
Identifiers
URN: urn:nbn:se:gih:diva-4521DOI: 10.1152/ajpcell.00099.2016ISI: 000384749700010PubMedID: 27486093OAI: oai:DiVA.org:gih-4521DiVA: diva2:951273
Available from: 2016-08-08 Created: 2016-08-08 Last updated: 2017-03-31Bibliographically approved

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Ekblom, BjörnLarsen, Filip J
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Björn Ekblom's research groupResearch group for Mitokondriell funktion och metabolisk kontroll
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CiteExportLink to record
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Citation style
  • apa
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  • modern-language-association-8th-edition
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