Skeletal muscle mitochondrial respiration in AMPKα2 kinase-dead mice.

Abstract

AIM To study whether the phenotypical characteristics (exercise intolerance; reduced spontaneous activity) of the AMPKα2 kinase-dead (KD) mice can be explained by a reduced mitochondrial respiratory flux rates (JO(2) ) in skeletal muscle. Secondly, the effect of the maturation process on JO(2) was studied. METHODS In tibialis anterior (almost exclusively type 2 fibres) muscle from young (12-17 weeks, n = 7) and mature (25-27 weeks, n = 12) KD and wild-type (WT) (12-17 weeks, n = 9; 25-27 weeks, n = 11) littermates, JO(2) was quantified in permeabilized fibres ex vivo by respirometry, using a substrate-uncoupler-inhibitor-titration (SUIT) protocol: malate, octanoyl carnitine, ADP and glutamate (GMO(3) ), + succinate (GMOS(3) ), + uncoupler (U) and inhibitor (rotenone) of complex I respiration. Citrate synthase (CS) activity was measured as an index of mitochondrial content. RESULTS Citrate synthase activity was highest in young WT animals and lower in KD animals compared with age-matched WT. JO(2) per mg tissue was lower (P < 0.05) in KD animals (state GMOS(3) ). No uncoupling effect was seen in any of the animals. Normalized oxygen flux (JO(2) /CS) revealed a uniform pattern across the SUIT protocol with no effect of KD. However, JO(2) /CS was higher [GMO(3) , GMOS(3) , U and rotenone (only WT)] in the mature compared with the young mice - irrespective of the genotype (P < 0.05). CONCLUSION Exercise intolerance and reduced activity level seen in KD mice may be explained by reduced JO(2) in the maximally coupled respiratory state. Furthermore, an enhancement of oxidative phosphorylation capacity per mitochondrion is seen with the maturation process.

DOI: 10.1111/j.1748-1716.2011.02399.x

Cite this paper

@article{Larsen2012SkeletalMM, title={Skeletal muscle mitochondrial respiration in AMPKα2 kinase-dead mice.}, author={Severin Olesen Larsen and Jonas M\oller Kristensen and Nis Ottesen Stride and J\orgen F P Wojtaszewski and J\orn Wulff Helge and Flemming Dela}, journal={Acta physiologica}, year={2012}, volume={205 2}, pages={314-20} }