Le 2012 Abstract Bioblast

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Le CH, Hocker AD, Dreyer HC, Roach RC, Gnaiger E, Chicco AJ (2012) Two-week acclimatization to 5200m markedly alters substrate utilization and increases OXPHOS efficiency, with no effect on respiratory capacity in skeletal muscle mitochondria. Mitochondr Physiol Network 17.12.

Link: MiPNet17.12 Bioblast 2012 - Open Access

Le CH, Hocker AD, Dreyer HC, Roach RC, Gnaiger E, Chicco AJ (2012)

Event: Bioblast 2012

Catherine Le

Previous research examining the effects of high-altitude hypoxia on muscle mitochondrial function has been primarily limited to morphological and biochemical analyses [1]. The aim of this study was to comprehensively examine the effects of short-term acclimatization to 5200m on skeletal muscle mitochondrial respiratory function. Vastus lateralis samples were obtained from 15 healthy subjects (8 male, 7 female 21 ± 2 yrs of age) from Eugene, OR prior to and following 16 days atop Mt. Chacaltaya in the Bolivian Andes. Mitochondrial respiratory function was determined in permeabilized muscle fibers by high-resolution respirometry using a variety of substrate, uncoupler, and inhibitor combinations. Respirometric analysis revealed marked elevations in phosphorylation rates with all substrates (maximal complex I+II) following altitude acclimatization, with a 31% increased reliance on CI vs. CII respiration (S-Rot) and no significant effect on total ETS capacity/mg of tissue (FCCP uncoupled rate). This resulted in a 39% improvement in OXPHOS efficiency with all substrates (P<0.001). Strikingly, OXPHOS efficiency (P/E) with palmitoylcarnitine + malate was increased by 79% (P<3.78E-06), with less robust improvements with pyruvate + malate. Interestingly, there was nearly a 100% decreased contribution of glutamate oxidation in the presence of saturating supply of both fat and carbohydrate substrates, and a 56% reduction when combined with pyruvate alone (P<0.001 and P<0.05, respectively). Taken together, these data indicate that 16 days of exposure to 5200m markedly alters muscle mitochondrial substrate utilization and improves OXPHOS efficiency without eliciting any significant effect on muscle respiratory capacity.

  1. Levett DZ, Radford EJ, Menassa DA, Graber EF, Morash AJ, Hoppeler H, Clarke K, Martin DS, Ferguson-Smith AC, Montgomery HE, Grocott MP, Murray AJ, Caudwell Xtreme Everest Research Group (2012) Acclimatization of skeletal muscle mitochondria to high-altitudehypoxia during an ascent of Everest. FASEB J 26: 1431-­1441.

Keywords: Skeletal muscle, Hypoxia, Oxygraph-2k

O2k-Network Lab: US CO Fort Collins Chicco AJ


Labels:

Stress:Ischemia-reperfusion  Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Regulation: Fatty acid  Coupling state: OXPHOS, ETS  Pathway: N, S  HRR: Oxygraph-2k 




Affiliations and author contributions

Catherine H Le (1), Austin D Hocker (3), Hans C Dreyer (3), Robert C Roach (4), Erich Gnaiger (5), Adam J Chicco (1, 2)

(1) Cell and Molecular Biology, Colorado State University, Fort Collins, CO, USA; Email: catherinele@me.com

(2) Health and Exercise Science, Colorado State University, Fort Collins, CO, USA

(3) University of Oregon, Eugene, OR, USA

(4) Altitude Research Center, University of Colorado Denver, Aurora, CO, USA

(5) Medical University of Innsbruck, Innsbruck, Austria


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