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Difference between revisions of "Gnaiger 2019 MiP2019"

From Bioblast
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“''Preventable diseases are strongly related to a sedentary life style. These are spreading world-wide at an epidemic scale. Mitochondrial dysfunction is increasingly associated with the progression of such pathologies: cause or consequence? There is currently no regimented, quantitative system, or database organized to routinely test, compare and monitor mitochondrial capacities within individuals, populations, or among populations. This reflects the need for scientific innovation and represents a shortcoming in the health system of our modern, rapidly aging society''” (MitoEAGLE COST Action application). The working groups of the COST Action CA15203 have made substantial progress towards meeting the mission of Mitochondrial Fitness Mapping (Fig. 1). The present communication (''1'') provides an example of harmonization of datasets published by different research laboratories on OXPHOS capacity in isolated mitochondria and permeabilized fibers obtained from biopsies of human skeletal muscle (''vastus lateralis''); (''2'') emphasizes the importance of comparative protocol harmonization projects and reproducibility studies; (''3'') illustrates the necessity and difficulty of defining objective exclusion criteria and applying quality assessment of published data; (''4'') links muscle mitochondrial fitness to whole body aerobic fitness; (''5'') discusses the extension of tissue-specific to systemic mitochondrial fitness from muscle to brain; and (''6'') documents the added value of Open Access data repositories.
“''Preventable diseases are strongly related to a sedentary life style. These are spreading world-wide at an epidemic scale. Mitochondrial dysfunction is increasingly associated with the progression of such pathologies: cause or consequence? There is currently no regimented, quantitative system, or database organized to routinely test, compare and monitor mitochondrial capacities within individuals, populations, or among populations. This reflects the need for scientific innovation and represents a shortcoming in the health system of our modern, rapidly aging society''” (MitoEAGLE COST Action application). The working groups of the COST Action CA15203 have made substantial progress towards meeting the mission of Mitochondrial Fitness Mapping (Fig. 1). The present communication (''1'') provides an example of harmonization of datasets published by different research laboratories on OXPHOS capacity in isolated mitochondria and permeabilized fibers obtained from biopsies of human skeletal muscle (''vastus lateralis''); (''2'') emphasizes the importance of comparative protocol harmonization projects and reproducibility studies; (''3'') illustrates the necessity and difficulty of defining objective exclusion criteria and applying quality assessment of published data; (''4'') links muscle mitochondrial fitness to whole body aerobic fitness; (''5'') discusses the extension of tissue-specific to systemic mitochondrial fitness from muscle to brain; and (''6'') documents the added value of Open Access data repositories.


Analogous to ergometric measurement of ''V''<sub>O2max</sub> on a cycle or treadmill, cell ergometry is based on measurement of OXPHOS-capacity, ''J''O<sub>2,P</sub> [pmol O<sub>2</sub>·s<sup>-1</sup>·mg<sup>-1</sup>] equivalent to [µmol O<sub>2</sub>·s<sup>1</sup>·kg<sup>1</sup>], at the mitochondrial level. The main datasets on OXPHOS capacity of isolated mitochondria or permeabilized muscle fibers, harmonization algorithms, and exclusion criteria applied in the present analysis have been reviewed ten years ago (Gnaiger 2009). Only a few more studies published since then were integrated. This is intended to initiate a comprehensive review by the MitoEAGLE Working Group 2 (skeletal muscle). Harmonization introduces potential biases with a scope of improvement based on updated evaluation of (1) wet/dry mass ratios applicable to studies reporting dry mass only; (2) flux control ratios applied to calculate combined NADH- and succinate-linked OXPHOS capacities from data limited to the NADH-pathway or succinate-pathway capacities measured separately; (3) temperature adjustment for measurements at temperatures different from 37 °C [Lemieux et al 2017]; (4) oxygen limitation of measurements with permeabilized fibers that are performed at or below air saturation [Pesta and Gnaiger 2012]; (5) OXPHOS capacities reported without evaluation of saturating concentrations of ADP, P<sub>i</sub>, and fuel substrates, or without concern of stable steady-state fluxes; and (6) potential bias when results are reported without details on instrumental O<sub>2</sub>-background tests, calibrations, and corresponding corrections.
Analogous to ergometric measurement of ''V''<sub>O2max</sub> on a cycle or treadmill, cell ergometry is based on measurement of OXPHOS-capacity, ''J''O<sub>2,P</sub> [pmol O<sub>2</sub>·s<sup>-1</sup>·mg<sup>-1</sup>] equivalent to [µmol O<sub>2</sub>·s<sup>1</sup>·kg<sup>1</sup>], at the mitochondrial level. The main datasets on OXPHOS capacity of isolated mitochondria or permeabilized muscle fibers, harmonization algorithms, and exclusion criteria applied in the present analysis have been reviewed ten years ago [1]. Only a few more studies published since then were integrated. This is intended to initiate a comprehensive review by the MitoEAGLE Working Group 2 (skeletal muscle). Harmonization introduces potential biases with a scope of improvement based on updated evaluation of (1) wet/dry mass ratios applicable to studies reporting dry mass only; (2) flux control ratios applied to calculate combined NADH- and succinate-linked OXPHOS capacities from data limited to the NADH-pathway or succinate-pathway capacities measured separately; (3) temperature adjustment for measurements at temperatures different from 37 °C [2]; (4) oxygen limitation of measurements with permeabilized fibers that are performed at or below air saturation [3]; (5) OXPHOS capacities reported without evaluation of saturating concentrations of ADP, P<sub>i</sub>, and fuel substrates, or without concern of stable steady-state fluxes; and (6) potential bias when results are reported without details on instrumental O<sub>2</sub>-background tests, calibrations, and corresponding corrections.


Recent trends of an increasing body mass index (BMI) of the human population indicate an epidemic prevalence of obesity in many countries despite the fact that underweight remains the dominant problem in the world’s poorest regions (NCD-RisC 2017). Extending the concept of the ‘Reference Man’ (Sender et al 2016), a healthy reference population (HRP) is defined with a large range of body height (standing height, ''h'') and corresponding reference body mass, ''m''°, reference ''V''<sub>O2max</sub>°, and mitochondrial fitness parameters. The reference mass/height relationship constitutes a basic component of the concept of the HRP, obtained from >17.000 measurements on healthy people reported between 1931 and 1944  before the fast food and soft drink epidemic, with about half of the reported measurements ranging from 1.2 to 1.8 m corresponding to ''m''° of 22 to 68 kg and ''h''/''m''<sup>0.35</sup> (Zucker 1962). The relative body mass index, ''rBMI'', at height ''h'' is defined as the actual body mass, ''m'', relative to the reference body mass, ''m''°, at the same height of the HRP. Deviations of ''m'' versus ''m''° are due to weight gain without height gain. OXPHOS capacity per mass of vastus lateralis declines as a power function of ''rBMI''. ''V''<sub>O2max</sub>/BM can be predicted as a function of (''1'') the metabolically inactive body weight added to a person at height ''h'', (''2'') the decline of mitochondrial capacity per muscle mass as a consequence of an inactive lifestyle and increased body weight, and (''3'') a slight increase of muscle mass with increasing ''rBMI'' as a ‘weight lifting effect’. The consequences of the mitochondrial control on ''V''<sub>O2max/BM</sub> will be discussed in terms of mechanistic explanations of a large range of neurodegenerative diseases related to the passive lifestyle.
Recent trends of an increasing body mass index (BMI) of the human population indicate an epidemic prevalence of obesity in many countries despite the fact that underweight remains the dominant problem in the world’s poorest regions [4]. Extending the concept of the ‘Reference Man’ [5], a healthy reference population (HRP) is defined with a large range of body height (standing height, ''h'') and corresponding reference body mass, ''m''°, reference ''V''<sub>O2max</sub>°, and mitochondrial fitness parameters. The reference mass/height relationship constitutes a basic component of the concept of the HRP, obtained from >17.000 measurements on healthy people reported between 1931 and 1944  before the fast food and soft drink epidemic, with about half of the reported measurements ranging from 1.2 to 1.8 m corresponding to ''m''° of 22 to 68 kg and ''h''/''m''<sup>0.35</sup> [6]. The relative body mass index, ''rBMI'', at height ''h'' is defined as the actual body mass, ''m'', relative to the reference body mass, ''m''°, at the same height of the HRP. Deviations of ''m'' versus ''m''° are due to weight gain without height gain. OXPHOS capacity per mass of vastus lateralis declines as a power function of ''rBMI''. ''V''<sub>O2max</sub>/BM [7] can be predicted as a function of (''1'') the metabolically inactive (compared to ''V''<sub>O2max</sub>) body weight added to a person at height ''h'', (''2'') the decline of mitochondrial capacity per muscle mass as a consequence of an inactive lifestyle and increased body weight, and (''3'') a slight increase of muscle mass with increasing ''rBMI'' as a ‘weight lifting effect’. The consequences of the mitochondrial control on ''V''<sub>O2max/BM</sub> will be discussed in terms of mechanistic explanations of a large range of neurodegenerative diseases related to the passive lifestyle with an increased ''rBMI'' [8].
|editor=[[Plangger M]], [[Tindle-Solomon L]]
|editor=[[Plangger M]], [[Tindle-Solomon L]]
|mipnetlab=AT Innsbruck Gnaiger E, AT Innsbruck MitoFit, AT Innsbruck Oroboros
|mipnetlab=AT Innsbruck Gnaiger E, AT Innsbruck MitoFit, AT Innsbruck Oroboros
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== References ==
== References ==
:::#  
:::# Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837-45. - [[Gnaiger 2009 Int J Biochem Cell Biol |»Bioblast link«]]
:::# Lemieux H, Blier PU, Gnaiger E (2017) Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers. Sci Rep 7:2840. - [[Lemieux 2017 Sci Rep |»Bioblast link«]]
:::# 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. - [[Pesta 2012 Methods Mol Biol |»Bioblast link«]]
:::# NCD Risk Factor Collaboration (NCD-RisC) (2017) Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 390:2627–42.
:::# Sender R, Fuchs S, Milo R (2016) Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 14:e1002533.
:::# Zucker TF (1962) Regression of standing and sitting weights on body weight: man. In: Altman PL, Dittmer DS, eds: Growth including reproduction and morphological development. Committee on Biological Handbooks, Fed Amer Soc Exp Biol:336-7.
:::# Loe H, Rognmo Ø, Saltin B, Wisløff U (2013) Aerobic capacity reference data in 3816 healthy men and women 20-90 years. PLoS One 8:e64319.
:::# Gnaiger E (2019) Weight gain relative to the body mass index of a healthy reference population related to aerobic capacity and mitochondrial fitness. MitoFit Preprint Arch doi:10.26124/mitofit:190004.
 
 


== Figures ==
== Figures ==

Revision as of 02:35, 9 October 2019

Erich Gnaiger
OXPHOS capacity in human muscle tissue and body mass index – the MitoEAGLE mission towards an integrative database.

Link: MiP2019

Gnaiger E (2019)

Event: MiP2019

COST Action MitoEAGLE

Preventable diseases are strongly related to a sedentary life style. These are spreading world-wide at an epidemic scale. Mitochondrial dysfunction is increasingly associated with the progression of such pathologies: cause or consequence? There is currently no regimented, quantitative system, or database organized to routinely test, compare and monitor mitochondrial capacities within individuals, populations, or among populations. This reflects the need for scientific innovation and represents a shortcoming in the health system of our modern, rapidly aging society” (MitoEAGLE COST Action application). The working groups of the COST Action CA15203 have made substantial progress towards meeting the mission of Mitochondrial Fitness Mapping (Fig. 1). The present communication (1) provides an example of harmonization of datasets published by different research laboratories on OXPHOS capacity in isolated mitochondria and permeabilized fibers obtained from biopsies of human skeletal muscle (vastus lateralis); (2) emphasizes the importance of comparative protocol harmonization projects and reproducibility studies; (3) illustrates the necessity and difficulty of defining objective exclusion criteria and applying quality assessment of published data; (4) links muscle mitochondrial fitness to whole body aerobic fitness; (5) discusses the extension of tissue-specific to systemic mitochondrial fitness from muscle to brain; and (6) documents the added value of Open Access data repositories.

Analogous to ergometric measurement of VO2max on a cycle or treadmill, cell ergometry is based on measurement of OXPHOS-capacity, JO2,P [pmol O2·s-1·mg-1] equivalent to [µmol O2·s1·kg1], at the mitochondrial level. The main datasets on OXPHOS capacity of isolated mitochondria or permeabilized muscle fibers, harmonization algorithms, and exclusion criteria applied in the present analysis have been reviewed ten years ago [1]. Only a few more studies published since then were integrated. This is intended to initiate a comprehensive review by the MitoEAGLE Working Group 2 (skeletal muscle). Harmonization introduces potential biases with a scope of improvement based on updated evaluation of (1) wet/dry mass ratios applicable to studies reporting dry mass only; (2) flux control ratios applied to calculate combined NADH- and succinate-linked OXPHOS capacities from data limited to the NADH-pathway or succinate-pathway capacities measured separately; (3) temperature adjustment for measurements at temperatures different from 37 °C [2]; (4) oxygen limitation of measurements with permeabilized fibers that are performed at or below air saturation [3]; (5) OXPHOS capacities reported without evaluation of saturating concentrations of ADP, Pi, and fuel substrates, or without concern of stable steady-state fluxes; and (6) potential bias when results are reported without details on instrumental O2-background tests, calibrations, and corresponding corrections.

Recent trends of an increasing body mass index (BMI) of the human population indicate an epidemic prevalence of obesity in many countries despite the fact that underweight remains the dominant problem in the world’s poorest regions [4]. Extending the concept of the ‘Reference Man’ [5], a healthy reference population (HRP) is defined with a large range of body height (standing height, h) and corresponding reference body mass, m°, reference VO2max°, and mitochondrial fitness parameters. The reference mass/height relationship constitutes a basic component of the concept of the HRP, obtained from >17.000 measurements on healthy people reported between 1931 and 1944 before the fast food and soft drink epidemic, with about half of the reported measurements ranging from 1.2 to 1.8 m corresponding to m° of 22 to 68 kg and h/m0.35 [6]. The relative body mass index, rBMI, at height h is defined as the actual body mass, m, relative to the reference body mass, m°, at the same height of the HRP. Deviations of m versus m° are due to weight gain without height gain. OXPHOS capacity per mass of vastus lateralis declines as a power function of rBMI. VO2max/BM [7] can be predicted as a function of (1) the metabolically inactive (compared to VO2max) body weight added to a person at height h, (2) the decline of mitochondrial capacity per muscle mass as a consequence of an inactive lifestyle and increased body weight, and (3) a slight increase of muscle mass with increasing rBMI as a ‘weight lifting effect’. The consequences of the mitochondrial control on VO2max/BM will be discussed in terms of mechanistic explanations of a large range of neurodegenerative diseases related to the passive lifestyle with an increased rBMI [8].


Bioblast editor: Plangger M, Tindle-Solomon L O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck MitoFit, AT Innsbruck Oroboros


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Affiliations

Oroboros Instruments, Innsbruck, Austria
Dept Visceral, Transplant Thoracic Surgery, Daniel Swarovski Research Lab, Medical Univ Innsbruck, Austria

References

  1. Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837-45. - »Bioblast link«
  2. Lemieux H, Blier PU, Gnaiger E (2017) Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers. Sci Rep 7:2840. - »Bioblast link«
  3. 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. - »Bioblast link«
  4. NCD Risk Factor Collaboration (NCD-RisC) (2017) Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 390:2627–42.
  5. Sender R, Fuchs S, Milo R (2016) Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 14:e1002533.
  6. Zucker TF (1962) Regression of standing and sitting weights on body weight: man. In: Altman PL, Dittmer DS, eds: Growth including reproduction and morphological development. Committee on Biological Handbooks, Fed Amer Soc Exp Biol:336-7.
  7. Loe H, Rognmo Ø, Saltin B, Wisløff U (2013) Aerobic capacity reference data in 3816 healthy men and women 20-90 years. PLoS One 8:e64319.
  8. Gnaiger E (2019) Weight gain relative to the body mass index of a healthy reference population related to aerobic capacity and mitochondrial fitness. MitoFit Preprint Arch doi:10.26124/mitofit:190004.


Figures