Gnaiger 2011 Abstract-MonteVerita

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Gnaiger E (2011) Mitochondrial respiratory capacity at maximum aerobic exercise levels: Are intracellular oxygen levels limiting? Abstract Monte Verita.

Link: The impact of hypoxia on cells, mice and men

Gnaiger E (2011)

Event: Monte Verita

Mitochondrial capacity: OXPHOS capacity is evaluated in isolated mitochondria (mt) and permeabilized cells with physiological substrate cocktails to reconstitute tricarboxylic acid cycle function. As a consequence, convergent electron flow from Complexes CI+II of the electron transfer system (ETS) to the Q-junction exerts an additive effect on flux [1].

Oxygen kinetics of mt-respiration: The apparent Km,O2 or c50 [µM] (p50 [kPa]) of mt-respiration increases linearly with respiratory capacity controlled by metabolic state, from 0.2 to 1.6 µM determined by high-resolution respirometry. O2 gradients are significant only in large cells including cardiomyocytes. The apparent p50 increases 100-fold in permeabilized muscle fibers due to diffusion gradients [2].

mt-function at VO2max: Aerobic capacity of the human leg muscle exceeds maximum O2 uptake of isolated mitochondria [3] and v. lateralis during VO2max [4]. Therefore, oxygen supply limits aerobic performance, proportional to the apparent mt-excess capacity [5]. mt-respiration is more sensitive to average pO2 in heterogenous tissues than under homogenous conditions in vitro. Tissue heterogeneity increases the kinetic dependence of flux on average intracellular pO2. High mt-density reinforces the steepness of oxygen gradients and oxygen heterogeneity in the tissue, contributing to the O2 limitation in athletic vs sedentary individuals at VO2max [6]. This provides a functional rationale for the observation that hypoxia does not specifically trigger mt-biogenesis [7].

Contribution to K-Regio MitoCom Tyrol.

[1] Gnaiger 2009; Lemieux et al 2011 Int J Biochem Cell Biol

[2] Gnaiger 2003; Scandurra, Gnaiger 2010 Adv Exp Med Biol.

[3] Rasmussen et al 2001 AJP.

[4] Boushel et al 2011 Mitochondrion.

[5] Gnaiger et al 1998 JEB.

[6] Richardson et al; Haseler et al JAP.

[7] Pesta et al 2011 AJP; Jacobs et al 2011 JAP.

MiPNetLab: AT Innsbruck Gnaiger E

Labels: MiParea: Respiration Mammal;model: Human  Regulation: Oxygen kinetics, Substrate Coupling state: OXPHOS Substrate state: CI, CII, CI&II HRR: Oxygraph-2k 

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