The Molecular Bases of Training Adaptation

Coffey, Vernon G.; Hawley, John A.

doi:10.2165/00007256-200737090-00001

Cited by 554 publications

(474 citation statements)

References 426 publications

Supporting

Mentioning

418

Contrasting

Unclassified

Order By: Relevance

“…In this way, a controlled expression of those proteins involved in the regulation of substrate oxidation, substrate transport and mitochondrial fusion and fission collectively occur in the hours and days following each successive exercise training bout, providing the exercise stimulus is sufficient in terms of intensity and duration [11]. The acute post-translational modifications of cell signalling kinases, the downstream localisation of their associated transcription factors and the subsequent increase in messenger RNA (mRNA) transcripts of their target genes is therefore considered to form the molecular basis of training adaptation [12].…”

mentioning

confidence: 99%

The Emerging Role of p53 in Exercise Metabolism

Bartlett

Drust

et al. 2013

Sports Med

View full text Add to dashboard Cite

The major tumour suppressor protein, p53, is one of the most well-studied proteins in cell biology. Often referred to as the Guardian of the Genome, the list of known functions of p53 include regulatory roles in cell cycle arrest, apoptosis, angiogenesis, DNA repair and cell senescence. More recently, p53 has been implicated as a key molecular player regulating substrate metabolism and exercise-induced mitochondrial biogenesis in skeletal muscle. In this context, the study of p53 therefore has obvious implications for both human health and performance, given that impaired mitochondrial content and function is associated with the pathology of many metabolic disorders such as ageing, type 2 diabetes, obesity and cancer, as well as reduced exercise performance. Studies on p53 knockout (KO) mice collectively demonstrate that ablation of p53 content reduces intermyofibrillar (IMF) and subsarcolemmal (SS) mitochondrial yield, reduces cytochrome c oxidase (COX) activity and peroxisome proliferator-activated receptor gamma co-activator 1-a protein content whilst also reducing mitochondrial respiration and increasing reactive oxygen species production during state 3 respiration in IMF mitochondria. Additionally, p53 KO mice exhibit marked reductions in exercise capacity (in the magnitude of 50 %) during fatiguing swimming, treadmill running and electrical stimulation protocols. p53 may regulate contractile-induced increases in mitochondrial content via modulating mitochondrial transcription factor A (Tfam) content and/or activity, given that p53 KO mice display reduced skeletal muscle mitochondrial DNA, Tfam messenger RNA and protein levels. Furthermore, upon muscle contraction, p53 is phosphorylated on serine 15 and subsequently translocates to the mitochondria where it forms a complex with Tfam to modulate expression of mitochondrial-encoded subunits of the COX complex. In human skeletal muscle, the exercise-induced phosphorylation of p53 Ser15 is enhanced in conditions of reduced carbohydrate availability in association with enhanced upstream signalling through 5 0 adenosine monophosphateactivated protein kinase but not p38 mitogen-activated protein kinase. In this way, undertaking regular exercise in carbohydrate restricted states may therefore be a practical approach to achieve the physiological benefits of consistent p53 signalling. Although our knowledge of p53 in exercise metabolism has advanced considerably, much of our current understanding of p53 regulation and associated targets is derived from various non-muscle cells and tissues. As such, many fundamental questions remain unanswered in contracting skeletal muscle. Detailed studies concerning the time-course of p53 activation (including additional post-translational modifications and subsequent subcellular translocation), as well as the effects of exercise modality (endurance versus resistance), intensity, duration, fibre type, age, training status and nutrient availability, must now be performed so that we can optimise exercise prescription guideli...

show abstract

mentioning

confidence: 99%

The Emerging Role of p53 in Exercise Metabolism

Bartlett

Drust

et al. 2013

Sports Med

View full text Add to dashboard Cite

show abstract

“…Furthermore, EDL muscles from the same hosts do not show immunochemical evidence of a fast twitch (type II myosin) to slow twitch (type I myosin) transition (Table 5). The latter finding distinguishes the response of Dmp1-cre Mbtps1 cKO muscle from that expected after endurance training (50).…”

Section: Discussionmentioning

confidence: 77%

Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age

Gorski

Huffman

Vallejo³

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Conditional deletion of Mbtps1 (cKO) protease in bone osteocytes leads to an age-related increase in mass (12%) and in contractile force (30%) in adult slow twitch soleus muscles (SOL) with no effect on fast twitch extensor digitorum longus muscles. Surprisingly, bone from 10 -12-month-old cKO animals was indistinguishable from controls in size, density, and morphology except for a 25% increase in stiffness. cKO SOL exhibited increased expression of Pax7, Myog, Myod1, Notch, and Myh3 and 6-fold more centralized nuclei, characteristics of postnatal regenerating muscle, but only in type I myosin heavy chain-expressing cells. Increased expression of gene pathways mediating EGF receptor signaling, circadian exercise, striated muscle contraction, and lipid and carbohydrate oxidative metabolism were also observed in cKO SOL. This muscle phenotype was not observed in 3-month-old mice. Although Mbtps1 mRNA and protein expression was reduced in cKO bone osteocytes, no differences in Mbtps1 or cre recombinase expression were observed in cKO SOL, explaining this age-related phenotype. Understanding bone-muscle cross-talk may provide a fresh and novel approach to prevention and treatment of age-related muscle loss.Bone osteocytes are multifunctional endocrine cells. Osteoid osteocytes control bone mineralization by secretion of DMP1, phosphate-regulating endopeptidase homolog, X-linked (PHEX), and matrix extracellular phosphoglycoprotein (MEPE) (1), whereas mature osteocytes secrete sclerostin, an inhibitor of bone formation, and regulate phosphate homeostasis and, indirectly, bone mineralization via production of FGF23 (2). Osteocytes are the mechanosensory cells in bone and appear to regulate muscle function and myogenesis (3-5). Specifically, deletion of connexin43 in osteoblasts/osteocytes shows it is involved in postnatal bone-muscle cross-talk via an osteocalcin-mediated stimulation of muscle formation and function (5). Differentiated muscle cells, in return, secrete as yet unidentified factors that protect osteocytes against apoptosis and produce a factor that synergizes with fluid flow shear stress to increase prostaglandin E 2 production by osteocytes (6). Myogenesis in adult muscle occurs via activation of satellite (stem) cells during muscle regeneration after injury or exercise-induced damage (7,8). Distinct populations of satellite cells appear to be responsible for regeneration of fast twitch and slow twitch myofibers (9, 10), respectively. MBTPS1 (SKI-1, PCSK8, S1P) 3 is the eighth member of the proprotein convertase family of proteases (11). Localized to the cis/medial Golgi, MBTPS1 catalyzes the mandatory first cleavage of transmembrane-bound transcription factors like SREBP1 and cAMP-response element-binding protein; once released, their DNA binding domains are imported into the nucleus where they regulate transcription (12). Interestingly, MBTPS1 is required for the transcription of a number of bone matrix and mineralization-related genes including type XI collagen, Phex, Dmp1, fibronectin, and fibrillin ...

show abstract

“…1). Presumably this AMPK regulated increase in PGC-1α enhances mitochondrial biogenesis, thus resulting in long term adaptations that enhance the rate of ATP production (Aschenbach et al, 2004;Coffey & Hawley, 2007).…”

Section: Amp/atp Ratiomentioning

confidence: 99%

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

Ihsan¹,

Watson²,

Abbiss³

2014

Cell Mol Exerc Physiol

View full text Add to dashboard Cite

PGC-1α is regarded as a key regulator of mitochondrial biogenesis due to its central role in regulating the activity of key transcription factors associated with encoding mitochondrial components. Additionally, PGC-1α has shown to mediate adaptations that increase fat metabolism and angiogenesis, contributing to the overall oxidative phenotype of the muscle. While it is well established that exercise is a potent stimulator of PGC-1α, recent evidence indicates that heat and cold exposures may also influence mitochondrial biogenesis through the up-regulation of PGC-1α. This highlights the potential use of these modalities in conjunction with exercise to enhance training adaptations. As such, the purpose of this review is to describe the possible mechanisms and pathways by which exercise, as well as hot and cold exposures may influence mitochondrial biogenesis. It is clear that changes in intracellular calcium, oxidative stress and phosphorylation potential are major up-regulators of PGC-1α during exercise. Moreover, there is evidence implicating calcium signalling, in addition to β-adrenergic activation in cold-induced mitochondrial biogenesis, while PGC-1α during heat exposure is likely triggered by changes in phosphorylation potential and nitric oxide signalling. However, these mechanisms appear to change considerably when cold/heat is administered following exercise, and seem to be dependent on the experimental models used (i.e. in vitro vs. in vivo, rodent vs. human). Understanding the effects heat/cold exposure and its interaction with exercise may lead to the optimisation and development of temperature-related interventions to enhance training adaptations, or aid in the treatment of mitochondrial related diseases.

show abstract

The Molecular Bases of Training Adaptation

Cited by 554 publications

References 426 publications

The Emerging Role of p53 in Exercise Metabolism

The Emerging Role of p53 in Exercise Metabolism

Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) Gene in Osteocytes Stimulates Soleus Muscle Regeneration and Increased Size and Contractile Force with Age

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

Contact Info

Product

Resources

About