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Difference between revisions of "Gnaiger 2019 MiP2019"

From Bioblast
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|event=MiP2019
|event=MiP2019
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MitoEAGLE]]
“Diseases that are strongly related to a sedentary life style 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.
“Diseases that are strongly related to a sedentary life style 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 [”mol O2·s-1·kg1], 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, 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.
Analogous to ergometric measurement of V<sub>O2max</sub> on a cycle or treadmill, cell ergometry is based on measurement of OXPHOS-capacity, JO<sub>2,P</sub> [pmol O<sub>2</sub>·s<sup>-1</sup>·mg<sup>-1</sup>] equivalent to [”mol 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.


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 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 (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. VO2max/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 VO2max/BM 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 (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/m0.35 (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</sub>/BM will be discussed in terms of mechanistic explanations of a large range of neurodegenerative diseases related to the passive lifestyle.
|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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::::Oroboros Instruments, Innsbruck, Austria
::::Oroboros Instruments, Innsbruck, Austria
::::Dept Visceral, Transplant Thoracic Surgery, Daniel Swarovski Research Lab, Medical Univ Innsbruck, Austria
::::Dept Visceral, Transplant Thoracic Surgery, Daniel Swarovski Research Lab, Medical Univ Innsbruck, Austria
== References ==

Revision as of 14:00, 2 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

“Diseases that are strongly related to a sedentary life style 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 [”mol 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 (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, 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 (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 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 (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. VO2max/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 VO2max/BM will be discussed in terms of mechanistic explanations of a large range of neurodegenerative diseases related to the passive lifestyle.


‱ 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