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

TY - JOUR

T1 - Exercise training increases skeletal muscle mitochondrial volume density by enlargement of existing mitochondria and not de novo biogenesis

AU - Lundby, Anne-Kristine Meinild

AU - Jacobs, R A

AU - Gehrig, S

AU - de Leur, J

AU - Hauser, M

AU - Bonne, Thomas Christian

AU - Flück, Daniela

AU - Dandanell, Sune

AU - Kirk, N

AU - Kaech, A

AU - Ziegler, U

AU - Larsen, Steen

AU - Lundby, Carsten

PY - 2018

Y1 - 2018

N2 - Aims: (i) To determine whether exercise-induced increases in muscle mitochondrial volume density (MitoVD) 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 MitoVD. 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: MitoVD 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+IIP) or cytochrome c oxidase (COX) activity. Correlations were found between MitoVD 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 MitoVD and CS activity only (P = 0.04; R = 0.49). Intrinsic respiratory capacities decreased (P < 0.05) with training when respiration was normalized to MitoVD. This was not the case when normalized to CS activity although the percentage change was comparable. Conclusions: MitoVD was increased by inducing mitochondrial enlargement rather than de novo biogenesis. CS activity may be appropriate to track training-induced changes in MitoVD.

AB - Aims: (i) To determine whether exercise-induced increases in muscle mitochondrial volume density (MitoVD) 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 MitoVD. 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: MitoVD 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+IIP) or cytochrome c oxidase (COX) activity. Correlations were found between MitoVD 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 MitoVD and CS activity only (P = 0.04; R = 0.49). Intrinsic respiratory capacities decreased (P < 0.05) with training when respiration was normalized to MitoVD. This was not the case when normalized to CS activity although the percentage change was comparable. Conclusions: MitoVD was increased by inducing mitochondrial enlargement rather than de novo biogenesis. CS activity may be appropriate to track training-induced changes in MitoVD.

KW - Adaptations

KW - Mitochondria

KW - Muscle

KW - Training

KW - Volume density

U2 - 10.1111/apha.12905

DO - 10.1111/apha.12905

M3 - Journal article

C2 - 28580772

AN - SCOPUS:85021792645

SN - 1748-1708

VL - 222

JO - Acta Physiologica

JF - Acta Physiologica

IS - 1

M1 - e12905

ER -