Exercise training increases skeletal muscle mitochondrial volume density by enlargement of existing mitochondria and not de novo biogenesis

Abstract

Aims: (i) To determine whether exercise-induced increases in muscle mitochondrial volume density (Mito_VD ) are related to enlargement of existing mitochondria or de novo biogenesis and (ii) to establish whether measures of mitochondrial-specific enzymatic activities are valid biomarkers for exercise-induced increases in Mito_VD .

Method: Skeletal muscle samples were collected from 21 healthy males prior to and following 6 weeks of endurance training. Transmission electron microscopy was used for the estimation of mitochondrial densities and profiles. Biochemical assays, western blotting and high-resolution respirometry were applied to detect changes in specific mitochondrial functions.

Result: Mito_VD increased with 55 ± 9% (P < 0.001), whereas the number of mitochondrial profiles per area of skeletal muscle remained unchanged following training. Citrate synthase activity (CS) increased (44 ± 12%, P < 0.001); however, there were no functional changes in oxidative phosphorylation capacity (OXPHOS, CI+II_P ) or cytochrome c oxidase (COX) activity. Correlations were found between Mito_VD and CS (P = 0.01; r = 0.58), OXPHOS, CI+CIIP (P = 0.01; R = 0.58) and COX (P = 0.02; R = 0.52) before training; after training, a correlation was found between Mito_VD and CS activity only (P = 0.04; R = 0.49). Intrinsic respiratory capacities decreased (P < 0.05) with training when respiration was normalized to Mito_VD. This was not the case when normalized to CS activity although the percentage change was comparable_. CONCLUSIONS: Mito_VD was increased by inducing mitochondrial enlargement rather than de novo biogenesis. CS activity may be appropriate to track training-induced changes in Mito_VD.

Keywords: adaptations; mitochondria; muscle; training; volume density.