Control of human energy expenditure by cytochrome c oxidase subunit IV-2.
Am J Physiol Cell Physiol
; 311(3): C452-61, 2016 09 01.
Article
en En
| MEDLINE
| ID: mdl-27486093
ABSTRACT
Resting metabolic rate (RMR) in humans 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. Overexpression 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 toward both oxidative stress, and severe hypoxia compared with 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Complejo IV de Transporte de Electrones
/
Metabolismo Energético
Tipo de estudio:
Health_economic_evaluation
Límite:
Adult
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Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article