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Fifteen days of moderate normobaric hypoxia does not affect mitochondrial function, and related genes and proteins, in healthy men

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Abstract

Purpose

To investigate within the one study potential molecular and cellular changes associated with mitochondrial biogenesis following 15 days of exposure to moderate hypoxia.

Methods

Eight males underwent a muscle biopsy before and after 15 days of hypoxia exposure (FiO2 = 0.140–0.154; ~ 2500–3200 m) in a hypoxic hotel. Mitochondrial respiration, citrate synthase (CS) activity, and the content of genes and proteins associated with mitochondrial biogenesis were investigated.

Results

Our main findings were the absence of significant changes in the mean values of CS activity, mitochondrial respiration in permeabilised fibers, or the content of genes and proteins associated with mitochondrial biogenesis, after 15 days of moderate normobaric hypoxia.

Conclusion

Our data provide evidence that 15 days of moderate normobaric hypoxia have negligible influence on skeletal muscle mitochondrial content and function, or genes and proteins content associated with mitochondrial biogenesis, in young recreationally active males. However, the increase in mitochondrial protease LON content after hypoxia exposure suggests the possibility of adaptations to optimise respiratory chain function under conditions of reduced O2 availability.

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Data availability

The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AMS:

Acute mountain sickness

ATP:

Adenosine triphosphate

BIOPS:

Biopsy preservation solution

BMI:

Body Mass Index

CI:

Confidence interval

CI to CV:

Complex I–V

COX:

Cytochrome c oxidase

CS:

Citrate synthase

E:

Electron transport system capacity

ES:

Effect size

ETC:

Electron transport chain

FCCP:

Titrating carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone

FiO2 :

Fractional inspired oxygen

Hb:

Hemoglobin

Hct:

Hematocrit

HIF-1:

Hypoxia-inducible factor 1

L:

Leak respiration

LONP:

Lon Protease

MIRO5:

Mitochondrial respiration medium

P:

Oxidative phosphorylation capacity

p53:

Tumor suppressor protein

PGC-1α:

Peroxisome proliferator-activated receptor γ coactivator 1α

Post:

After 15 days of hypoxic exposure

Pre:

Before 15 days of hypoxic exposure

ROX:

Residual oxygen consumption

SaO2 :

Arterial blood saturation

SD:

Standard Deviation

SEM:

Standard Error

SL:

Sea level

TEM:

Transmission electron microscopy

V̇O2peak :

Peak oxygen uptake

Wpeak :

Peak power output

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Acknowledgements

The authors would like to acknowledge and thank all those who supervised participants while they stayed in the hypoxic hotel: Elise Brent, James Broatch, Remi Delfour-Peyrethon, Nir Eynon, Jackson Fyfe, Cian McGinley, and Sarah Voisin. We would also like to thank all the participants for volunteering for such a challenging project.

Funding

No funding was received for conducting this study.

Author information

Authors and Affiliations

  1. Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia

    Alessandra Ferri, Xu Yan, Jujiao Kuang, Cesare Granata, Rodrigo S. F. Oliveira, Christopher P. Hedges, Francois Billaut & David J. Bishop

  2. Department of Diabetes, Central Clinical School, Monash University, Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia

    Cesare Granata

  3. Human Performance Research Group, Federal University of Technology-Parana (UTFPR), Curitiba, Brazil

    Adriano E. Lima-Silva

  4. Département de Kinésiologie, Université Laval, Québec, Canada

    Francois Billaut

Authors
  1. Alessandra Ferri
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  2. Xu Yan
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  4. Cesare Granata
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  9. David J. Bishop
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Contributions

AF, FB, DJB: study design; AF, FB, AEL, DJB: sample acquisition; XY, JK, CG, RSFO, CPH: biochemical and data analyses; AF, XY, JK, CG, RSFO, CPH, AEL, DJB: data interpretation; AF, DJB: first draft of the manuscript; AF, CG, RSFO, CPH, AEL: editing of manuscript; AF, XY, JK, CG, RSFO, CPH, FB, AEL, DJB: manuscript approval.

Corresponding author

Correspondence to David J. Bishop.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This research study was approved by the Victoria University Human Research Ethics Committee (HRET 10/220). All procedures conformed to the standards set by the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Additional information

Communicated by Guido Ferretti

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Ferri, A., Yan, X., Kuang, J. et al. Fifteen days of moderate normobaric hypoxia does not affect mitochondrial function, and related genes and proteins, in healthy men. Eur J Appl Physiol 121, 2323–2336 (2021). https://doi.org/10.1007/s00421-021-04706-4

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