title: Mitochondrial oxygen affinity predicts basal metabolic rate in humans.
abstract: The basal metabolic rate (BMR) is referred to as the minimal rate of metabolism required to support basic body functions. It is well known that individual BMR varies greatly, even when correcting for body weight, fat content, and thyroid hormone levels, but the mechanistic determinants of this phenomenon remain unknown. Here, we show in humans that mass-related BMR correlates strongly to the mitochondrial oxygen affinity (p50(mito); R(2)=0.66, P=0.0004) measured in isolated skeletal muscle mitochondria. A similar relationship was found for oxygen affinity and efficiency during constant-load submaximal exercise (R(2)=0.46, P=0.007). In contrast, BMR did not correlate to overall mitochondrial density or to proton leak. Mechanistically, part of the p50(mito) seems to be controlled by the excess of cytochrome c oxidase (COX) protein and activity relative to other mitochondrial proteins. This is illustrated by the 5-fold increase in p50(mito) after partial cyanide inhibition of COX at doses that do not affect maximal mitochondrial electron flux through the ETS. These data suggest that the interindividual variation in BMR in humans is primarily explained by differences in mitochondrial oxygen affinity. The implications of these findings are discussed in terms of a trade-off between aerobic efficiency and power.
authors.affiliation: 1 Department of Physiology and Pharmacology, Karolinska Institutet, 11486 Stockholm, Sweden. filip.larsen@ki.se
authors.forename: Filip J
authors.initials: FJ
authors.lastname: Larsen
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Schiffer
authors.forename: Kent
authors.initials: K
authors.lastname: Sahlin
authors.forename: Björn
authors.initials: B
authors.lastname: Ekblom
authors.forename: Eddie
authors.initials: E
authors.lastname: Weitzberg
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
mesh_terms: D000328:Adult; D000818:Animals; D001481:Basal Metabolism / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D010101:Oxygen Consumption / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology; D018892:Proton-Motive Force; D013045:Species Specificity; D055815:Young Adult
chemical_list: D003576:Electron Transport Complex IV