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Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest

Citation

Levett, DZ and Radford, EJ and Menassa, DA and Graber, EF and Morash, AJ and Hoppeler, H and Clarke, K and Martin, DS and Ferguson-Smith, AC and Montgomery, HE and Grocott, MPW and Murray, AJ, Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest, The FASEB Journal, 26, (4) pp. 1431-1441. ISSN 0892-6638 (2012) [Refereed Article]

Copyright Statement

Copyright 2012 FASEB

DOI: doi:10.1096/fj.11-197772

Abstract

Ascent to high altitude is associated with a fall in the partial pressure of inspired oxygen (hypobaric hypoxia). For oxidative tissues such as skeletal muscle, resultant cellular hypoxia necessitates acclimatization to optimize energy metabolism and restrict oxidative stress, with changes in gene and protein expression that alter mitochondrial function. It is known that lowlanders returning from high altitude have decreased muscle mitochondrial densities, yet the underlying transcriptional mechanisms and time course are poorly understood. To explore these, we measured gene and protein expression plus ultrastructure in muscle biopsies of lowlanders at sea level and following exposure to hypobaric hypoxia. Subacute exposure (19 d after initiating ascent to Everest base camp, 5300 m) was not associated with mitochondrial loss. After 66 d at altitude and ascent beyond 6400 m, mitochondrial densities fell by 21%, with loss of 73% of subsarcolemmalmitochondria. Correspondingly, levels of the transcriptional coactivator PGC-1α fell by 35%, suggesting down-regulation of mitochondrial biogenesis. Sustained hypoxia also decreased expression of electron transport chain complexes I and IV and UCP3 levels. We suggest that during subacute hypoxia, mitochondria might be protected from oxidative stress. However, following sustained exposure, mitochondrial biogenesis is deactivated and uncoupling down-regulated, perhaps to improve the efficiency of ATP production.

Item Details

Item Type:Refereed Article
Keywords:metabolism, energetics
Research Division:Medical and Health Sciences
Research Group:Medical Biochemistry and Metabolomics
Research Field:Metabolic Medicine
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
Author:Morash, AJ (Dr Andrea Morash)
ID Code:94193
Year Published:2012
Web of Science® Times Cited:54
Deposited By:Research Division
Deposited On:2014-09-02
Last Modified:2014-09-23
Downloads:0

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