Alterations in mitochondrial fission and fusion proteins with chronic muscle use and disuse

Abstract

The maintenance of mitochondrial shape depends on reaching an equilibrium between fission and fusion. To investigate the role of fission and fusion regulatory proteins in mitochondrial biogenesis, the content of these proteins was evaluated in mitochondrial fractions and whole muscle of animals subjected to chronic muscle use and disuse. The tibialis anterior (TA) muscle of rats was subjected to either chronic contractile activity (CCA, 10Hz, 3 hours/day, 7 days) or denervation for 7 days. The contralateral limb of both sets of animals served as internal controls. With chronic disuse, the fission proteins Fis1 and Drp1 decreased by 1.9 and 1.3-fold, respectively. Furthermore, the expression of the fusion proteins Opa1 and Mfn2 was reduced in mitochondria by 6.3 and 4.2-fold, respectively. CCA had the opposite effects on the proteins governing mitochondria morphology, as 1.4 and 2.0-fold increases in Opa1 and Mfn2 were observed. However, Drp1 was unaffected by CCA, while Fis1 was increased by 1.5-fold. Thus, mitochondrial biogenesis appears to be associated with increases in the ratio of fusion:fission proteins, while the opposite is evident with muscle disuse. Supported by NSERC