Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects
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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 muscle oxidative capacity (OXPHOS).Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake (VO(2peak)) 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 fibers. Biomarkers of interest were citrate synthase (CS) activity, cardiolipin content, mitochondrial DNA content, 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 in VO(2peak) (range 29.9 -71.6 ml/min/kg) and in mitochondrial content (4-15% of cell volume). Cardiolipin content showed the strongest association to mitochondrial content followed by CS- and complex I activity. mtDNA was not related to mitochondrial content. Complex IV activity showed the strongest association to muscle oxidative capacity followed by complex II activity.We conclude that cardiolipin content, CS and complex I activity are the biomarkers that exhibit the strongest association to mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle.
|Journal||Journal of Physiology|
|Publication status||Published - 2012|