Unravelling the mechanisms regulating muscle mitochondrial biogenesis.

Skeletal muscle is a tissue with a low mitochondrial content under basal conditions, but it is responsive to acute increases in contractile activity patterns (i.e. exercise) which initiate the signalling of a compensatory response, leading to the biogenesis of mitochondria and improved organelle function. Exercise also promotes the degradation of poorly functioning mitochondria (i.e. mitophagy), thereby accelerating mitochondrial turnover, and preserving a pool of healthy organelles. In contrast, muscle disuse, as well as the aging process, are associated with reduced mitochondrial quality and quantity in muscle. This has strong negative implications for whole-body metabolic health and the preservation of muscle mass. A number of traditional, as well as novel regulatory pathways exist in muscle that control both biogenesis and mitophagy. Interestingly, although the ablation of single regulatory transcription factors within these pathways often leads to a reduction in the basal mitochondrial content of muscle, this can invariably be overcome with exercise, signifying that exercise activates a multitude of pathways which can respond to restore mitochondrial health. This knowledge, along with growing realization that pharmacological agents can also promote mitochondrial health independently of exercise, leads to an optimistic outlook in which the maintenance of mitochondrial and whole-body metabolic health can be achieved by taking advantage of the broad benefits of exercise, along with the potential specificity of drug action.

Mitochondria, muscle health, and exercise with advancing age.

Skeletal muscle health is dependent on the optimal function of its mitochondria. With advancing age, decrements in numerous mitochondrial variables are evident in muscle. Part of this decline is due to reduced physical activity, whereas the remainder appears to be attributed to age-related alterations in mitochondrial synthesis and degradation. Exercise is an important strategy to stimulate mitochondrial adaptations in older individuals to foster improvements in muscle function and quality of life.

Sugar flux through the flight muscles of hovering vertebrate nectarivores: a review.

In most vertebrates, uptake and oxidation of circulating sugars by locomotor muscles rises with increasing exercise intensity. However, uptake rate by muscle plateaus at moderate aerobic exercise intensities and intracellular fuels dominate at oxygen consumption rates of 50% of maximum or more. Further, uptake and oxidation of circulating fructose by muscle is negligible. In contrast, hummingbirds and nectar bats are capable of fueling expensive hovering flight exclusively, or nearly completely, with dietary sugar. In addition, hummingbirds and nectar bats appear capable of fueling hovering flight completely with fructose. Three crucial steps are believed to be rate limiting to muscle uptake of circulating glucose or fructose in vertebrates: (1) delivery to muscle; (2) transport into muscle through glucose transporter proteins (GLUTs); and (3) phosphorylation of glucose by hexokinase (HK) within the muscle. In this review, we summarize what is known about the functional upregulation of exogenous sugar flux at each of these steps in hummingbirds and nectar bats. High cardiac output, capillary density, and blood sugar levels in hummingbirds and bats enhance sugar delivery to muscles (step 1). Hummingbird and nectar bat flight muscle fibers have relatively small cross-sectional areas and thus relatively high surface areas across which transport can occur (step 2). Maximum HK activities in each species are enough for carbohydrate flux through glycolysis to satisfy 100 % of hovering oxidative demand (step 3). However, qualitative patterns of GLUT expression in the muscle (step 2) raise more questions than they answer regarding sugar transport in hummingbirds and suggest major differences in the regulation of sugar flux compared to nectar bats. Behavioral and physiological similarities among hummingbirds, nectar bats, and other vertebrates suggest enhanced capacities for exogenous fuel use during exercise may be more wide spread than previously appreciated. Further, how the capacity for uptake and phosphorylation of circulating fructose is enhanced remains a tantalizing unknown.