The Role Of Dynamin-related Protein 1 (drp1) In The Adaptations To Exercise

Abstract

Mitochondria are highly dynamic organelles within eukaryotic cells that function primarily to produce energy. Exercise has been known to positively impact mitochondria for over 50 years. Our previous work indicated that one novel factor, dynamin-related protein 1 (Drp1) that is responsible for splitting mitochondria, was impacted by exercise. However, it is not known whether Drp1 is essential for the development of exercise adaptations. PURPOSE: To determine the impact of reduced Drp1 expression in skeletal muscle on muscle strength, exercise performance, and long-term exercise induced adaptations. METHODS: For each protocol, skeletal muscle specific heterozygous (mDrp1+/-) and littermate control mice were used. Animals were sacrificed and tissues harvested at the times indicated. Protocol 1: Treadmill exercise at 15 m/min (5° grade) for 90 minutes for controls and 13 m/min for mDrp1+/- mice. Protocol 2: Thirty days of in cage voluntary wheel running (VWR) after which wheels were locked. Animals were sacrificed 30 hours later. Exercise effects were statistically assessed with two-way ANOVA or t-test (P<0.05 established a priori; values presented as mean ± SEM). RESULTS: Muscle strength was reduced in mDrp1+/- mice resulting in a reduction in protocol 1 exercise speed but not relative intensity. Following protocol 1, signaling molecules and cellular factors regulating mitochondrial life cycle were not different between mDrp1+/- and control exercised mice. Additional metabolites including plasma lactate and triglyceride and muscle glycogen levels post exercise were not different between groups. In untrained mice, endurance exercise capacity was not different between groups; however, following VWR, mDrp1+/- mice had a reduced increase in exercise capacity when compared to control trained mice. Several cellular factors and signaling molecules regulating mitochondrial life cycle showed similar expression levels in mDrp1+/- animals when compared to control exercise trained animals. CONCLUSIONS: Our results indicate that Drp1 is particularly important for muscle strength in untrained mice and may play a role in the improvement of exercise capacity.