Gnaiger 2009 Int J Biochem Cell Biol

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

Abstract

Maximal ADP-stimulated mitochondrial respiration depends on convergent electron flow through Complexes I+II to the Q-junction of the electron transport system (ETS). In most studies of respiratory control in mitochondrial preparations, however, respiration is limited artificially by supplying substrates for electron input through either Complex I or II. High-resolution respirometry with minimal amounts of tissue biopsy (1 to 3 mg wet weight of permeabilized muscle fibres per assay) provides a routine approach for multiple substrate-uncoupler-inhibitor titrations. Under physiological conditions, maximal respiratory capacity is obtained with glutamate+malate+succinate, reconstituting the operation of the tricarboxylic acid cycle and preventing depletion of key metabolites from the mitochondrial matrix. In human skeletal muscle, conventional assays with pyruvate+malate or glutamate+malate yield submaximal oxygen fluxes at 0.50 to 0.75 of capacity of oxidative phosphorylation (OXPHOS). Best estimates of muscular OXPHOS capacity at 37 °C [pmol O2∙s­-1∙mg-­1 wet weight] with isolated mitochondria or permeabilized fibres, suggest a range of 100 to 150 and up to 180 in healthy humans with normal body mass index and top endurance athletes, but reduction to 60 to 120 in overweight healthy adults with predominantly sedentary life style. The apparent ETS excess capacity (uncoupled respiration) over ADP-stimulated OXPHOS capacity is high in skeletal muscle of active and sedentary humans, but absent in mouse skeletal muscle. Such differences of mitochondrial quality in skeletal muscle are unexpected and cannot be explained at present. A comparative data base of mitochondrial physiology may provide the key for understanding the functional implications of mitochondrial diversity from mouse to man, and evaluation of altered mitochondrial respiratory control patterns in health and disease.

Keywords

Mitochondrial respiratory control, high-resolution respirometry, skeletal muscle, Q-cycle, Q-junction, electron transport, maximal oxygen consumption, pyruvate, glutamate, succinate, tricarboxylic acid cycle

Abbreviations

HRR, high-resolution respirometry; Imt, isolated mitochondria; Pfi, permeabilized fibers; Pmt, mitochondrial protein; SUIT, substrate-uncoupler-inhibitor-titration; TCA, tricarboxylic acid; u, uncoupled; Ww, wet weight (see also Tab. 1).

Comments

• "apparent ETS excess capacity (uncoupled respiration)": It will be helpful to distinguish physiological uncoupling and pathological dyscoupling from experimentally induced 'uncoupling' (using FCCP, DNP or other established uncouplers), by reference to the ETS state as the non-coupled state E of respiration [ MiPNet12.15 ]. Erich Gnaiger, 2010-08-20