Chicco 2016b Abstract MitoFit Science Camp 2016

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OXPHOS coupling efficiency of permeabilized muscle fibers predicts metabolic efficiency of subjects exercising at 5260 m.
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Adam Chicco

Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Hocker AD, Lovering AT, Subudhi AW, Roach RC (2016)

Event: MitoFit Science Camp 2016 Kuehtai AT

Whether mitochondrial adaptions influence high-altitude (HA) exercise performance and acclimatization is controversial. Many studies indicate that muscle mitochondrial content and functional capacity decline with prolonged HA exposure, while others suggest altered substrate utilization and improvements in coupling efficiency [1]. Conclusions are often based on changes in selected mitochondrial enzyme contents, and more recently, high resolution respirometry (HRR) studies, but to date no studies have attempted to integrate comprehensive assessments of mitochondrial protein expression, respiratory function and physical performance in the same individuals.

The present study evaluated vastus lateralis muscle biopsies from 14 subjects (7 M, 7 F; 21 ± 2 years) at near sea level (Eugene, Oregon, USA) and following 16 days at 5260 meters (Mt. Chacaltaya, Bolivia) combining HRR studies with an Oroboros Oxygraph (Innsbruck, AT) with targeted proteomic profiling and systemic physiological assessments obtained during the 2012 AltitudeOmics expedition. Muscle fiber bundles were freshly prepared and saponin permeabilized by established methods [2] for evaluation of mass-specific respiratory capacity and substrate control during oxidative phosphorylation (OXPHOS), as well as the extent of non-phosphorylating respiratory “leak” (LEAK) and the enzymatic capacity of the electron transfer-pathway (ET-pathway). Proteomic profiling of snap frozen muscle biopsies was performed by LC/MS/MS at Colorado State University.

Respirometry studies revealed significant elevations in the capacity and control of OXPHOS after high-altitude exposure, particularly using fatty acid (palmitoylcarnitine) versus carbohydrate (pyruvate) as substrates, with no significant change in tissue-mass specific ET capacity. Muscle proteomics revealed a selective remodeling of glycolytic and mitochondrial enzyme pathways, with significant increases, decreases and no change in mitochondrial proteins, even within individual membrane complexes. Interestingly, no strong relationships were observed between muscle respirometry outcomes and 5 km cycling time at HA, but higher OXPHOS coupling control factors [3] significantly predicted improvements in metabolic work efficiency (W/kcal; r = 0.52- 0.82). This was primarily explained by lower LEAK values, but neither LEAK nor OXPHOS measures correlated as strongly as their relative expression as flux control factors, which paralleled greater expression of mitochondrial phosphate carrier protein and some respiratory complex subunits.

These studies highlight the value of coupling control factors in HRR studies as potential predictors of metabolic efficiency, and illustrate the complexity of mitochondrial adaptations to high altitude. Results will be discussed in support of flux control factors as important components of HRR assessments of “Mito Fitness”, and against the existence of suitable mitochondrial “marker” enzymes for representing or normalizing functional outcomes of mitochondrial metabolism in muscle fibers.


O2k-Network Lab: US CO Fort Collins Chicco AJ, AT Innsbruck Gnaiger E, AT Innsbruck MitoFit, AT Innsbruck Oroboros


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N  HRR: Oxygraph-2k  Event: D2  MitoFit Science Camp 2016 

Affiliations

1-Dept Biomedical Sci, Colorado State Univ, USA; 2-Med Univ Innsbruck, Austria; 3-Univ Oregon, OR, USA; 4-Univ Colorado Denver, CO, USA. - chicco@cahs.colostate.edu

References

  1. Horscroft JA, Murray AJ (2014) Skeletal muscle energy metabolism in environmental hypoxia: climbing towards consensus. Extrem Physiol Med 3:19.
  2. Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopsies of human muscle. Methods Mol Biol 810:25-58.
  3. Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. Oroboros MiPNet Publications, Innsbruck:80 pp.