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Gnaiger 2011 Abstract-Berlin

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Gnaiger E (2011) Fewer mitochondrial - mitochondrial 'fever': Mitochondrial physiology and capacity of oxidative phosphorylation in active and sedentary life styles. Abstract-Berlin.

Β» Targeting mitochondria

Gnaiger E (2011) Abstract

Abstract: A tight relationship is described between mitochondrial respiratory capacity of human skeletal muscle and physical fitness, which quantifies the decline of respiratory function as the result of a sedentary life style in the progression towards obesity [1]. Tissue-OXPHOS capacity is the capacity of oxidative phosphorylation in skeletal muscle, which is the product of mitochondrial density and respiratory intensity (structure times function; i.e. mitochondrial marker per tissue mass times OXPHOS capacity per mitochondrial marker). Tissue-OXPHOS capacity per unit wet weight [pmol O2βˆ™s-1βˆ™mg-1] is measured directly in permeabilized muscle fibres, and high-resolution respirometry provides a routine approach under physiological conditions (37 Β°C; Complex I+II substrate combination) with minimal amounts of tissue biopsy (1 to 3 mg wet weight per assay) [2].


In healthy subjects varying from athletic to sedentary life styles, tissue-OXPHOS capacity of vastus lateralis increases linearly with maximum aerobic ergometric performance (VO2max) and declines steeply with body mass index (BMI=body mass per body height squared [kg/m2]) in the range of 180 to 60 pmol O2βˆ™s-1βˆ™mg-1. The tissue-OXPHOS/BMI relationship spans from endurance athletes and physically active subjects (normal BMI 20-25), overweight individuals (BMI 25-30) with predominantly sedentary life style, to obese patients who are qualified as healthy controls in studies of type 2 diabetes (BMI >30). Total muscle tissue is unchanged or increases rather than decreases with higher BMI, whereas over-proportionally reduced mitochondrial density per muscle mass explains the loss of aerobic ergometric performance in the sedentary life style and development of obesity. Mitochondrial quality (OXPHOS capacity per mitochondrial marker) is largely maintained, but fatty acid oxidation capacity and coupling control decline as a result of diminishing exercise [2]. Specific mitochondrial injuries accumulate as a consequence of reduced mitochondrial density and correspondingly low mitochondrial turnover.


Based on the tissue-OXPHOS/BMI relationship and integrating known mechanisms responsible for dysregulation of mitochondrial biosynthesis under conditions of chronic low-grade inflammation, low mitochondrial density is a primary risk factor related to a wide range of degenerative diseases, including type 2 diabetes. The health benefits are emphasized of maintaining muscle mitochondrial density high, particularly with progressive age, as achieved by a physically active and nutritionally normal life style. The diagnostic perspective gained from analysis of mitochondrial competence after exercise training2 challenges the definition of the control group [3]: Are sedentary subjects healthy?


Contribution to K-Regio MitoCom Tyrol.

1. Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int. J. Biochem. Cell Biol. 41: 1837–1845.

2. Pesta D, Hoppel F, Macek C, Messner H, Faulhaber M, Kobel C, Parson W, Burtscher M, Schocke M, Gnaiger E (2011) Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. doi: 10.1152/ajpregu.00285.2011

3. Martin B, Ji S, Maudsley S, Mattson MP (2010) "Control" laboratory rodents are metabolically morbid: why it matters. Proc. Natl. Acad. Sci. USA 107: 6127-6133.


β€’ O2k-Network Lab: AT Innsbruck Gnaiger E


Labels:

Stress:Hypoxia  Organism: Human  Tissue;cell: Skeletal Muscle"Skeletal Muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.  Preparation: Permeabilized Cell or Tissue; Homogenate"Permeabilized Cell or Tissue; Homogenate" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.  Enzyme: TCA Cycle and Matrix Dehydrogenases"TCA Cycle and Matrix Dehydrogenases" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property., Complex I, Complex II; Succinate Dehydrogenase"Complex II; Succinate Dehydrogenase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property., Marker Enzyme"Marker Enzyme" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property.  Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Mitochondrial Biogenesis; Mitochondrial Density"Mitochondrial Biogenesis; Mitochondrial Density" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Substrate; Glucose; TCA Cycle"Substrate; Glucose; TCA Cycle" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Fatty Acid"Fatty Acid" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. 


HRR: Oxygraph-2k