title: Twenty-eight days at 3454-m altitude diminishes respiratory capacity but enhances efficiency in human skeletal muscle mitochondria.
abstract: Modifications of skeletal muscle mitochondria following exposure to high altitude (HA) are generally studied by morphological examinations and biochemical analysis of expression. The aim of this study was to examine tangible measures of mitochondrial function following a prolonged exposure to HA. For this purpose, skeletal muscle biopsies were obtained from 8 lowland natives at sea level (SL) prior to exposure and again after 28 d of exposure to HA at 3454 m. High-resolution respirometry was performed on the muscle samples comparing respiratory capacity and efficiency. Exercise capacity was assessed at SL and HA. Respirometric analysis revealed that mitochondrial respiratory capacity diminished in complex I- and complex II-specific respiration in addition to a loss of maximal state-3 oxidative phosphorylation capacity from SL to HA, all independent from alterations in mitochondrial content. Leak control coupling, respiratory control ratio, and oligomycin-induced leak respiration, all measures of mitochondrial efficiency, improved in response to HA exposure. SL respiratory capacities correlated with measures of exercise capacity near SL, whereas mitochondrial efficiency correlated best with exercise capacity following HA. This data demonstrate that 1 mo of exposure to HA reduces respiratory capacity in human skeletal muscle; however, the efficiency of electron transport improves.
authors.affiliation: Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Jacobs
authors.forename: Christoph
authors.initials: C
authors.lastname: Siebenmann
authors.forename: Mike
authors.initials: M
authors.lastname: Hug
authors.forename: Marco
authors.initials: M
authors.lastname: Toigo
authors.forename: Anne-Kristine
authors.initials: AK
authors.lastname: Meinild
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
mesh_terms: D000328:Adult; D000531:Altitude; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005080:Exercise Test; D006801:Humans; D016014:Linear Models; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000502:physiology; D015656:Respiratory Mechanics / Q000502:physiology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase