Aerobic Exercise/Endurance Training Relationship of mitochondria and aerobic exercise Mitochondria influences activities that last longer than a minute. There are different skeletal muscles fibers involved depending on the type of exercise being performed. With endurance training, mitochondrial content has the ability to increase due to both motor units being involved. Skeletal Muscle Fiber Types 3 Categories: Slow-twitch red fibers (Type I) contain the largest amount of mitochondria. The significance of the mitochondria in slow-twitch fibers allow for individuals to exercise for longer periods of time. These fibers have a low sacroplasmic reticulum progression, which means they will not release much Calcium or uptake a large amount of it. The role of calcium will be elaborated on later in this section. The slow-twitch fiber is most involved in aerobic exercise/endurance training. Essentially, they generate low levels of power that last over a long period of time. 4, 10, 17 Fast –twitch fibers (Type II) are the fiber type more involved in anaerobic exercise. They generate high levels of power over a short period of time. 2 types: Fast-twitch A and Fast-twitch B. Both types of these fibers have a high sacroplasmic reticulum progression, which means they have the ability of releasing a large amount of Calcium as well as being able to uptake a large amount. Fast-twitch A is the fiber type referred to as “fast-twitch red.” Type A can be recruited for aerobic or anaerobic exercise. Fast-twitch A fibers contain a moderate amount of mitochondria in comparison with the other fiber types. Fast-twitch B is the fiber type referred to as “fast-twitch white.” Type B is recruited more for anaerobic exercise. Fast-twitch B fibers contains the smallest amount of mitochondria in comparison with the other fiber types. The small amount of mitochondria allow for the individual to perform short bursts of exercise such as weight lifters. 4, 10, 17 Important to Note: Mitochondria are red and the muscle fibers obtain their color due to the mitochondrial content.10 The table below categorizes each type of fiber and characteristics: 19 1 Aerobic Exercise/Endurance Training 2 Aerobic Exercise/Endurance Training http://www.google.com/imgresmgurl=http://classes.midlandstech.edu/carterp/Courses/bio210/chap09/ table%25209.2.jpg&imgrefurl=http://classes.midlandstech.edu/carterp/Courses/bio210/chap09/ lecture1.html&h=720&w=960&sz=79&tbnid=ZgU4bH3Qlp20JM:&tbnh=90&tbnw=120&zoom=1&usg=__kw0FAf3q_CAMqGtHb2X4hiz5nOw=&docid=VhNqaTV Background of Mitochondrial Biogenesis The study of mitochondrial biogenesis has expanded over the years. Advancements have been made in relation to the effects of endurance training as well as other factors that affect mitochondrial biogenesis. Essentially, the adaptations of mitochondria due to exercise involve molecular signaling, transcription, translation, and the importing of proteins. The image demonstrates the events that take place in the mitochondria when mitochondria biogenesis occurs:10 3 Aerobic Exercise/Endurance Training 4 Aerobic Exercise/Endurance Training The figure below shows an overall summary of mitochondrial biogenesis: 4 5 Aerobic Exercise/Endurance Training 6 Aerobic Exercise/Endurance Training Influence of Aerobic Exercise on Mitochondrial Biogenesis Research has shown that trained individuals have a higher capacity of mitochondria in their skeletal muscle compared to untrained individuals.10 The diagram illustrates the differences in mitochondria capacity between untrained and trained tissues: 4 7 Aerobic Exercise/Endurance Training Figure 6-13 Eletron micrographs of mitochondria in tissues of (a) untrained and (b) trained rats. Mitochondria in trained animals appear to be more numerous, probably because there is a more elaborate mitochondrial reticulum. Micrographs courtesy of P.D. Gollnick. 8 Aerobic Exercise/Endurance Training The table below illustrates a study performed on rats of the effects on mitochondria in response to endurance training. It is displayed that the mitochondria in the trained muscle doubled in capacity compared to the untrained muscle.4 9 Aerobic Exercise/Endurance Training The table below shows the effects on muscle mass and activity of enzymes with endurance training: 4 10 Aerobic Exercise/Endurance Training Endurance training enables a stimulus to occur in the mitochondria that increases proteins causing replication. Mitochondrial biogenesis in an active muscle is thought to be integrated by local signals due to the adaptations being able to occur in only contracting muscles. The initial amount of mitochondrial content the individual has will determine the amount of biogenesis that occurs. Endurance training causes an increase in mitochondrial density, size and content due to repeated exercise. The shape and size changes have been noted in the subsarcolemmal and intermyofibrillar regions in the mitochondria after several weeks of exercise sessions, which expands the mitochondrial reticulum. The content of mitochondria has the ability to increase up to 100% for an individual who has been training for about a month. The occurrence of mitochondrial biogenesis allows for an increase in mitochondrial content, which benefits the individual by improving performance for training. There is greater allowance for going through the TCA cycle when more mitochondria are available. 4, 10, 11, 16, 18 More information on the effect of Aerobic Exercise on Mitochondrial Biogenesis can be found here: http://www.ncbi.nlm.nih.gov/pubmed/8818195 11 Aerobic Exercise/Endurance Training http://www.ncbi.nlm.nih.gov/pubmed/12959619 Physiologic benefit of training The effect of aerobic exercise causes an increase in mitochondrial content. The increase of mitochondria allows for improved oxygen consumption for tissues as well as the furnishing of ATP. Due to endurance training and mitochondrial biogenesis, endurance performance is enhanced and the individual is less susceptible to fatigue as fast as an untrained individual. 10, 24 More information on the Physiologic benefit of training on Mitochondrial Biogenesis can be found here: http://jap.physiology.org/content/111/4/1066.long Differences in types of training (i.e. interval training, etc.) Endurance training, a continuous type of exercise being completed at a low or moderate intensity for a long duration, has been the exercise most frequently studied in relation to mitochondrial biogenesis. The advancements in research being made in mitochondrial biogenesis have allowed for the study of the effects with other types of exercise. High intensity interval training, sprinting, and resistance training have all elicited to mitochondrial biogenesis.10,15 A study conducted by Medical Science of Sports Exercise on repeated-sprint exercise investigated effects of mitochondrial biogenesis. There were different factors that occurred in mitochondrial biogenesis that were evaluated in the study to determine if repeated-sprint training affects the increase of mitochondria. Signaling processes and the proteins involved were assessed as well as the effects from the repeated-sprint exercise on mRNA expression and protein abundance. The study also focused on the effects of PGC-1alpha, a main regulator of mitochondrial biogenesis, hypothesizing that this type of training would increase that protein. It was determined that several proteins increased during this exercise bout including: ACC, CaMK II, and PGC-1alpha suggesting that adaptations of mitochondrial biogenesis are apparent in short-term, high intensity exercise.23 More information on the effect of Repeated Sprints on Mitochondrial Biogenesis can be found here: http://www.ncbi.nlm.nih.gov/pubmed/22089482 A study conducted by The Journal of Applied Physiology on resistance training after endurance training assessed the effects of signaling and proteins involved in mitochondrial biogenesis. The stimulation of rapamycin (mTOR) occurs with resistance training fueling muscle growth and protein synthesis. Increases 12 Aerobic Exercise/Endurance Training of mRNA and PDK4 were noted following both bouts of exercise, suggesting initiation of mitochondrial biogenesis. The study had hypothesized the signaling response would decrease when adding resistance exercise to follow a bout of endurance exercise. However, the study found the signaling of expression genes and protein activation for protein synthesis in mitochondrial biogenesis was heightened. The results of the study suggest that resistance training is another form of exercise that also stimulates mitochondrial biogenesis.27 More information on the effect of Resistance exercise on Mitochondrial Biogenesis can be found here: http://jap.physiology.org/content/111/5/1335.long PGC-1alpha protein influence on biogenesis during endurance exercise Of the 3 PGC-coactivators, PCG-1alpha was discovered first. Expression of PCG-1alpha is synchronized by 3 kinases including: mitogen-activated protein kinase (MAPK), AMP-activated protein kinase, and calcium/ calmodulin-dependent protein kinase II (CaMKII). PCG-1alpha is pertinent to the function and regulation of mitochondrial content. PCG-1alpha takes on important roles within the mitochondria including: biogenesis, respiration, and function. The protein, PCG-1alpha, has the ability to coactivate several transcription factors, which leads to the transactivation of genes involved in the Electron Transport Chain and transcription factors of mtDNA. The encoding of an assortment of genes by the nucleus is coordinated by PGC-1alpha, resulting in mitochondrial biogenesis. The expression of the PGC-1alpha mRNA protein is mostly in tissues relied on for oxidative metabolism for ATP production. Single and chronic exercise sessions have made notable effects on PGC-1alpha mRNA and protein levels. The increases of mitochondrial biogenesis correlate with the upregulation of PGC-1alpha mRNA and protein levels. Increased cellular respiration and the transformation of fast-to-slow fiber types are the benefits of increasing PGC-1alpha at the protein level. A deficiency of PGC-1alpha causes a decline in mitochondrial content, respiratory function, and a decline in endurance performance. However, endurance training is not completely reliant on this protein. There is belief there are compensatory proteins that replace PGC-1alpha when needed to allow mitochondrial biogenesis to occur. 10, 15 More information on the influence of PGC-1alpha-protein on Mitochondrial Biogenesis can be found here:22, 24 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0041817 http://jap.physiology.org/content/111/4/1066.long The diagram below offers a visual aid of the role PGC-1alpha during mitochondria biogenesis: 10 13 Aerobic Exercise/Endurance Training 14 Aerobic Exercise/Endurance Training Role of Calcium and ATP Endurance training results in a greater number of mitochondria, and therefore, a greater capacity to maintain ATP due to an increase in oxygen uptake. During exercise, this is an important factor because if ATP levels are not maintained, muscle cells fatigue quickly. A higher rate of ATP/ADP ratio allows for an escalation in oxygen consumption when there is high capacity of mitochondria. 4, 10 The role of ATP is similar for untrained and trained individuals during mitochondrial biogenesis. In the intermembrane space of the mitochondria, an abundance of protons conducts the ATPase reaction forming ADP. ATP levels are maintained through the CPK, glycolytic flux and mitochondrial respiration, which are activated by ADP. A myokinase reaction can be initiated by the conversion of ATP and AMP from ADP. The pathway from this point is dependent upon the type of muscle fiber. In a trained individual, the increased amount of ATP causes a reduction in several processes including: phosphocreatine, glycolysis and lactic acid production, AMP and NH3 formation, and AMPK activation. The reduction of the several processes caused by the increase of ATP results in enhanced performanced. 4, 10 In mitochondrial biogenesis, the two contributing factors that follow the exercise session include Calcium ion and ATP turnover. Both factors can affect the mitochondrial production of ATP. The rate of ATP turnover is elevated with activity and elicits a change in energy status within the cell. The change in energy status can also be accomplished without exercise by mtDNA reduction. An increase of calcium is distinguished when there is disorder in ATP production within the mitochondria. The SR releases Calcium, activating kinases and phosphatases, which activates transcription factors. These transcription factors impact the encoding of mitochondrial proteins by way of the nuclear genes. The mitochondrial chemiosmotic gradient is also affected by the release of calcium due to the gradient binding and activating 15 Aerobic Exercise/Endurance Training TCA cycle dehydrogenases. Exercise causes AMP to elevate and activates AMPK-active protein kinase. Other kinase proteins are activated causing possible activation of nuclear transcription factors. Peroxisome proliferators-activated receptors-alpha and –y are other transcription factors involved in the process. The receptors and other transcription factors are believed to play a role in the binding of genes in association with coding for subunits of cytochrome oxidase and mitochondrial free fatty acid uptake. Understanding how some of these factors affect mitochondrial biogenesis is still unclear. 4, 10 More information on the role of ATP in Mitochondrial Biogenesis can be found here: 15 http://www.ncbi.nlm.nih.gov/pubmed/19448716 The image below illustrates the pathways of ATP in mitochondrial biogenesis: 10 Conclusion 16 Aerobic Exercise/Endurance Training Mitochondrial biogenesis contributes to aerobic exercise significantly. Slow-twitch fibers are the type of fiber recruited for endurance training. The occurrence of mitochondrial biogenesis allows for the increase of mitochondria enabling enhanced performance for the individual. The adaptations of mitochondria are made through molecular signaling, transcription, translation, and the importing of proteins. The influence of the PGC-1alpha protein was found to be the main stimulator protein of mitochondrial biogenesis. ATP levels are also relevant because the levels must be maintained to allow mitochondrial biogenesis to take place. Studies on other types of exercises have been conducted to evaluate mitochondrial biogenesis’ role. The studies found training other than endurance also stimulates mitochondrial biogenesis for enhanced performance. Overall, mitochondrial biogenesis is essential in aerobic exercise because it allows the individual’s training performance to excel. 17
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