title: Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects.
abstract: Skeletal muscle mitochondrial content varies extensively between human subjects. Biochemical measures of mitochondrial proteins, enzyme activities and lipids are often used as markers of mitochondrial content and muscle oxidative capacity (OXPHOS). The purpose of this study was to determine how closely associated these commonly used biochemical measures are to muscle mitochondrial content and OXPHOS. Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake (VO2peak) and muscle biopsies were obtained from the vastus lateralis. Mitochondrial content was determined using transmission electron microscopy imaging and OXPHOS was determined as the maximal coupled respiration in permeabilized fibres. Biomarkers of interest were citrate synthase (CS) activity, cardiolipin content, mitochondrial DNA content (mtDNA), complex I–V protein content, and complex I–IV activity. Spearman correlation coefficient tests and Lin's concordance tests were applied to assess the absolute and relative association between the markers and mitochondrial content or OXPHOS. Subjects had a large range of VO2peak (range 29.9–71.6ml min−1 kg−1) and mitochondrial content (4–15% of cell volume).Cardiolipin content showed the strongest association with mitochondrial content followed by CS and complex I activities. mtDNA was not related to mitochondrial content. Complex IV activity showed the strongest association with muscle oxidative capacity followed by complex II activity.We conclude that cardiolipin content, and CS and complex I activities are the biomarkers that exhibit the strongest association with mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle.
authors.affiliation: Center for Healthy Aging-Department of Biomedical Sciences, Copenhagen University, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Larsen
authors.forename: Joachim
authors.initials: J
authors.lastname: Nielsen
authors.forename: Christina Neigaard
authors.initials: CN
authors.lastname: Hansen
authors.forename: Lars Bo
authors.initials: LB
authors.lastname: Nielsen
authors.forename: Flemming
authors.initials: F
authors.lastname: Wibrand
authors.forename: Nis
authors.initials: N
authors.lastname: Stride
authors.forename: Henrik Daa
authors.initials: HD
authors.lastname: Schroder
authors.forename: Robert
authors.initials: R
authors.lastname: Boushel
authors.forename: Jørn Wulff
authors.initials: JW
authors.lastname: Helge
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
authors.forename: Martin
authors.initials: M
authors.lastname: Hey-Mogensen
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D002308:Cardiolipins / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D002950:Citrate (si)-Synthase / Q000032:analysis; D042967:Electron Transport Complex I / Q000032:analysis; D005080:Exercise Test; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D046529:Microscopy, Electron, Transmission; D008931:Mitochondria, Muscle / Q000737:chemistry* / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases; D018485:Muscle Fibers, Skeletal / Q000737:chemistry* / Q000648:ultrastructure; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D052097:Quadriceps Muscle / Q000737:chemistry* / Q000166:cytology
chemical_list: D015415:Biomarkers; D002308:Cardiolipins; D002352:Carrier Proteins; D008565:Membrane Proteins; D002950:Citrate (si)-Synthase; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I; C020439:oligomycin sensitivity-conferring protein