Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects

Steen Larsen, Joachim Nielsen, Christina Neigaard Hansen, Lars Bo Nielsen, Flemming Wibrand, Nis Ottesen Stride, Henrik Daa Schroder, Robert Christopher Boushel, Jørn Wulff Helge, Flemming Dela, Martin Hey-Mogensen

882 Citations (Scopus)

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.
Original languageEnglish
JournalJournal of Physiology
Volume590
Issue numberPt 14
Pages (from-to)3349-60
Number of pages12
ISSN0022-3751
DOIs
Publication statusPublished - 2012

Keywords

  • Adenosine Triphosphatases
  • Adult
  • Biological Markers
  • Cardiolipins
  • Carrier Proteins
  • Citrate (si)-Synthase
  • Electron Transport Complex I
  • Exercise Test
  • Humans
  • Male
  • Membrane Proteins
  • Microscopy, Electron, Transmission
  • Mitochondria, Muscle
  • Muscle Fibers, Skeletal
  • Oxidative Phosphorylation
  • Oxygen Consumption
  • Quadriceps Muscle

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