Mito-nuclear interactions modify Drosophila exercise performance

Abstract

Endurance exercise has received increasing attention as a broadly preventative measure against age-related disease and dysfunction. Improvement of mitochondrial quality by enhancement of mitochondrial turnover is thought to be among the important molecular mechanisms underpinning the benefits of exercise. Interactions between the mitochondrial and nuclear genomes are important components of the genetic basis for variation in longevity, fitness and the incidence of disease. Here, we examine the effects of replacing the mitochondrial genome (mtDNA) of several Drosophila strains with mtDNA from other strains, or from closely related species, on exercise performance. We find that mitochondria from flies selected for longevity increase the performance of flies from a parental strain. We also find evidence that mitochondria from other strains or species alter exercise performance, with examples of both beneficial and deleterious effects. These findings suggest that both the mitochondrial and nuclear genomes, as well as interactions between the two, contribute significantly to exercise capacity.

The effects of genetic background on exercise performance in Drosophila

“…The rate of age-related decline in climbing speed was measured by assessing the climbing speed of flies longitudinally over the course of 3 weeks [ 17 ] normalized to speed on the first day of climbing [ 17 ]. Similar to previously published data, we see significant differences in the rate of age-related decline in climbing speed between genotypes ( Figure 2c ), with w 1118 flies’ rate dropping to less than half of its initial starting point ( Figure 2c ; Table 1 ) [ 30 ].…”

“…In one study that compared the endurance of w 1118 , Oregon R, and Ra lines, w 1118 exercised flies performed similar to Ra exercised flies, with their endpoint endurance being similar [30]. However, Oregon R exercised flies ran longer than both the w 1118 and the Ra exercised lines [30]. To further investigate variation in commonly used wild-type lines during exercise training, we examined endurance and climbing ability of w 1118 and y 1 w 1 after training (Figure 3).…”

“…Longevity and endurance work in part through similar mechanisms [ 41 , 51 , 52 ]. Flies bred for longevity have better endurance than their parental line [ 30 ]. Microarrays revealed that breeding for longevity activated similar genes as those activated by endurance training [ 41 ], implying overlapping mechanisms between increased longevity and endurance.…”

“…There are differences in the climbing ability of different genetic backgrounds both pre- and post-exercise [ 16 , 21 , 22 , 30 , 35 ]. The RING assessment can measure acute climbing speed across ages [ 16 , 35 , 17 ].…”

Alpha- and beta-adrenergic octopamine receptors in muscle and heart are required for Drosophila exercise adaptations

“…After our 3 week training protocol, male flies increase climbing speed, cardiac stress resistance [11], endurance [12], flight performance [5], and lysosomal activity in their fat body [7]. Trained male flies have increased mitophagy in cardiac and skeletal muscle [13], increased mitochondrial enzyme activity [11,14] and changes in transcript expression similar to those found in long-lived flies [5]. These genetic and physiological adaptations closely resemble benefits seen in both rodent models [15] and humans [1].…”