title: Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle.
abstract: In human skeletal muscles, the current view is that the capacity for mitochondrial energy production, and thus endurance capacity, is set by the mitochondria volume. However, increasing the mitochondrial inner membrane surface comprises an alternative mechanism for increasing the energy production capacity. In the present study, we show that mitochondrial inner membranes in leg muscles of endurance-trained athletes have an increased ratio of surface per mitochondrial volume. We show a positive correlation between this ratio and whole body oxygen uptake and muscle fibre mitochondrial content. The results obtained in the present study help us to understand modulation of mitochondrial function, as well as how mitochondria can increase their oxidative capacity with increased demand.
  
  
  
  Mitochondrial energy production involves the movement of protons down a large electrochemical gradient via ATP synthase located on the folded inner membrane, known as cristae. In mammalian skeletal muscle, the density of cristae in mitochondria is assumed to be constant. However, recent experimental studies have shown that respiration per mitochondria varies. Modelling studies have hypothesized that this variation in respiration per mitochondria depends on plasticity in cristae density, although current evidence for such a mechanism is lacking. In the present study, we confirm this hypothesis by showing that, in human skeletal muscle, and in contrast to the current view, the mitochondrial cristae density is not constant but, instead, exhibits plasticity with long-term endurance training. Furthermore, we show that frequently recruited mitochondria-enriched fibres have significantly increased cristae density and that, at the whole-body level, muscle mitochondrial cristae density is a better predictor of maximal oxygen uptake rate than muscle mitochondrial volume. Our findings establish an elevating mitochondrial cristae density as a regulatory mechanism for increasing metabolic power in human skeletal muscle. We propose that this mechanism allows evasion of the trade-off between cell occupancy by mitochondria and other cellular constituents, as well as improved metabolic capacity and fuel catabolism during prolonged elevated energy requirements.
authors.affiliation: Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster, University of Southern Denmark, Odense, Denmark.|Department of Pathology, SDU Muscle Research Cluster, Odense University Hospital, Odense, Denmark.
authors.forename: Joachim
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster, University of Southern Denmark, Odense, Denmark.
authors.forename: Kasper D
authors.initials: KD
authors.lastname: Gejl
authors.affiliation: Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster, University of Southern Denmark, Odense, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Hey-Mogensen
authors.affiliation: Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
authors.forename: Hans-Christer
authors.initials: HC
authors.lastname: Holmberg
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Suetta
authors.affiliation: Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster, University of Southern Denmark, Odense, Denmark.|Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Krustrup
authors.affiliation: Department of Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Coen P H
authors.initials: CPH
authors.lastname: Elemans
authors.affiliation: Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster, University of Southern Denmark, Odense, Denmark.|Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
authors.forename: Niels
authors.initials: N
authors.lastname: Ørtenblad
mesh_terms: D000328:Adult; D000818:Animals; D004734:Energy Metabolism; D015444:Exercise; D005260:Female; D046369:Finches; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000648:ultrastructure*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D010101:Oxygen Consumption
keywords: electron microscopy; mitochondria; muscle metabolism; oxygen uptake; skeletal muscle