Transcriptional and post-transcriptional regulation of mitochondrial biogenesis in skeletal muscle: Effects of exercise and aging

Ljubicic, Vladimir; Joseph, Anna‐Maria; Saleem, Ayesha; Uguccioni, Giulia; Collu-Marchese, Melania; Lai, Ruanne Y J; Nguyen, Linda M.-D.; Hood, David A.

doi:10.1016/j.bbagen.2009.07.031

Cited by 150 publications

(118 citation statements)

References 182 publications

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“…Although the changes to existing PGC-1a activity co-ordinate the initial signalling pathways required to stimulate mitochondrial biogenesis, it is the subsequent increase in PGC-1a protein content that occurs with repeated exercise sessions that is therefore considered a necessary requirement to stimulate further mitochondrial adaptations during the course of an endurance training program [35]. For this reason, an understanding of the control of PGC-1a transcription is also important and, with this in mind, the reader is directed to several contemporary and excellent reviews [10,39,40].…”

Section: Regular Exercise Training Promotes Skeletal Muscle Mitochondmentioning

confidence: 99%

The Emerging Role of p53 in Exercise Metabolism

Bartlett

Drust

et al. 2013

Sports Med

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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...

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Section: Regular Exercise Training Promotes Skeletal Muscle Mitochondmentioning

confidence: 99%

The Emerging Role of p53 in Exercise Metabolism

Bartlett

Drust

et al. 2013

Sports Med

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“…Nuclear-encoded mitochondrial proteins, including mitochondrial transcription factors, are translated and synthesized in the cytosol as precursor proteins. It has been clarified that newly synthesized mitochondrial precursor proteins are transported into the mitochondria and refolded by mtHSP and HSP72 39) . Heat stress dramatically increases mtHSP and HSP72 protein contents in skeletal muscle 20,40) .…”

Section: Heat Stress Activates Regulatory Factors Of Mitochondrial Bimentioning

confidence: 99%

Heat stress induces mitochondrial adaptations in skeletal muscle

Tamura

Hatta

2017

JPFSM

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PURPOSE The purposes of present study were to investigate i) the chronic effects of whole‐body heat stress (WHS) on adaptation of mitochondrial enzyme activity and ii) the acute effects of WHS on kinase phosphorylation known to mediate mitochondrial biogenesis in mice skeletal muscle. METHODS ICR mice were divided into sedentary or WHS group. Mice in WHS group were exposed to hot environment chamber (30 × 20 × 13 cm, ambient temperature: 40 °C) for 30 min on each experiment day. In chronic experiment, we examined the effects of 3 weeks (Frequency: 5 days/week) WHS on maximal citrate synthase (CS) and 3‐Hydroxyacyl‐CoA dehydrogenase (3‐HAD) activities in plantaris muscle. In acute experiment, we studied the effects of a single WHS on phosphorylation of AMP activated protein kinase (AMPK), p38 mitrogen activated protein kinase (p38 MAPK) and calcium/calmodulin‐dependent protein kinase II (CaMK II) in plantaris muscle. RESULTS In chronic experiment, both maximal CS and 3‐HAD activities were increased in WHS group (CS: +35%, P<0.01, 3‐HAD: +49%, P<0.01). In acute experiment, phosphorylation of AMPK in WHS group was decreased (−43%, P<0.05). Phosphorylation of p38 MAPK was increased in WHS group (+252%, P<0.05). Phosphorylation of CaMK II was not different between groups. CONCLUSION Chronic whole‐body heat stress increased mitochondrial enzyme activities.

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“…The biosynthesis of the mitochondrion is a highly complex event that requires the coordinated and cooperative function of the nuclear and mitochondrial genomes (Goffart & Wiesner, 2003;Joseph et al, 2006). Indeed, the mitochondria proteome consists of over 1000 protein subunits (Goffart & Wiesner, 2003); of which, an estimated 90 to 95% are encoded in the nucleus and following translation in the cytosol, are subsequently transported into the mitochondrial compartments for assembly (Ljubicic et al, 2010). The remainder of mitochondrial proteins are encoded in the mitochondrion itself which possesses its own genome (mtDNA) (Ekstrand et al, 2004).…”

Section: Factors Involved In Mitochondrial Biogenesismentioning

confidence: 99%

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

Ihsan¹,

Watson²,

Abbiss³

2014

Cell Mol Exerc Physiol

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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.

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Transcriptional and post-transcriptional regulation of mitochondrial biogenesis in skeletal muscle: Effects of exercise and aging

Cited by 150 publications

References 182 publications

The Emerging Role of p53 in Exercise Metabolism

The Emerging Role of p53 in Exercise Metabolism

Heat stress induces mitochondrial adaptations in skeletal muscle

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

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