Exercise and Regulation of Protein Metabolism

Atherton, Philip J.; Phillips, Bethan E.; Wilkinson, Daniel J.

doi:10.1016/bs.pmbts.2015.06.015

Cited by 24 publications

(17 citation statements)

References 118 publications

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“…Understandably, the number of processes involved, together with the absence of a widely-accepted definition, results in a lack of consensus about which technique(s) can best assess mitochondrial biogenesis [28,29,34]. From its etymological meaning (i.e., the synthesis of new mitochondrial components), mitochondrial biogenesis can best be assessed by measuring the rate of mitochondrial protein synthesis (MitoPS) using stable isotopic tracers [28,35]. This technique however, seems to lack the ability, if used in isolation, to provide information regarding mitochondria remodeling, changes in mitochondrial content (the net outcome of MitoPS and MitoPB, with the latter also assessed using stable isotopic tracers [35]), mitochondrial respiratory function, and/or other aspects of mitochondrial quality [29,34].…”

Section: Mitochondrial Biogenesismentioning

confidence: 99%

“…From its etymological meaning (i.e., the synthesis of new mitochondrial components), mitochondrial biogenesis can best be assessed by measuring the rate of mitochondrial protein synthesis (MitoPS) using stable isotopic tracers [28,35]. This technique however, seems to lack the ability, if used in isolation, to provide information regarding mitochondria remodeling, changes in mitochondrial content (the net outcome of MitoPS and MitoPB, with the latter also assessed using stable isotopic tracers [35]), mitochondrial respiratory function, and/or other aspects of mitochondrial quality [29,34]. Therefore, while it has been argued that only measurements of the synthesis rate of mitochondrial proteins are indicative of mitochondrial biogenesis [28], a more comprehensive assessment of mitochondrial content, structure, quality, and respiratory function is required to put the results of mitochondrial biogenesis in context [29,36].…”

Section: Mitochondrial Biogenesismentioning

confidence: 99%

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Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

2018

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Physical inactivity represents the fourth leading risk factor for mortality, and it has been linked with a series of chronic disorders, the treatment of which absorbs ~ 85% of healthcare costs in developed countries. Conversely, physical activity promotes many health benefits; endurance exercise in particular represents a powerful stimulus to induce mitochondrial biogenesis, and it is routinely used to prevent and treat chronic metabolic disorders linked with sub-optimal mitochondrial characteristics. Given the importance of maintaining a healthy mitochondrial pool, it is vital to better characterize how manipulating the endurance exercise dose affects cellular mechanisms of exercise-induced mitochondrial biogenesis. Herein, we propose a definition of mitochondrial biogenesis and the techniques available to assess it, and we emphasize the importance of standardizing biopsy timing and the determination of relative exercise intensity when comparing different studies. We report an intensity-dependent regulation of exercise-induced increases in nuclear peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein content, nuclear phosphorylation of p53 (serine 15), and PGC-1α messenger RNA (mRNA), as well as training-induced increases in PGC-1α and p53 protein content. Despite evidence that PGC-1α protein content plateaus within a few exercise sessions, we demonstrate that greater training volumes induce further increases in PGC-1α (and p53) protein content, and that short-term reductions in training volume decrease the content of both proteins, suggesting training volume is still a factor affecting training-induced mitochondrial biogenesis. Finally, training-induced changes in mitochondrial transcription factor A (TFAM) protein content are regulated in a training volume-dependent manner and have been linked with training-induced changes in mitochondrial content.

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Section: Mitochondrial Biogenesismentioning

confidence: 99%

Section: Mitochondrial Biogenesismentioning

confidence: 99%

Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

2018

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“…Despite its widespread use in the literature, there is currently no widely-accepted definition of "mitochondrial biogenesis" (87,117) (a Google Scholar search for "mitochondrial biogenesis" returns > 60 000 hits) and this has contributed to confusion and conflicting interpretations about the effects of exercise on mitochondrial biogenesis. Given its etymological meaning (i.e., the synthesis of new mitochondrial components), it has been suggested that mitochondrial biogenesis can best be assessed by measuring the rate of mitochondrial protein synthesis (mitoPS) (1,87). However, a relationship between changes in mitoPS and subsequent changes in mitochondrial content (and/or respiratory function) remains to be established; this relationship cannot be assumed, especially as increases in muscle protein synthesis (MPS) following a single session of resistance exercise do not correlate with subsequent changes in muscle size in response to repeated resistance exercise sessions (i.e., exercise training) (80,89).…”

Section: Mitochondrial Biogenesismentioning

confidence: 99%

“…We acknowledge this classification is imperfect, and, as we discuss later, this lack of consensus on how to define high-intensity exercise is a major hurdle to reconciling some of the conflicting findings in the literature. 1 Longer GXTs will underestimate Ẇmax and the final power is typically referred to as peak power (Ẇpeak) (9). The measurement of exercise-induced changes in genes and proteins is not sufficient by itself as a measurement of mitochondrial biogenesis (i.e., the synthesis of new mitochondrial components) (87); nonetheless, these changes can provide an indication that mitochondrial biogenesis has been activated.…”

Section: High-intensity Exercise and Mitochondrial Biogenesis A) Defimentioning

confidence: 99%

High-Intensity Exercise and Mitochondrial Biogenesis: Current Controversies and Future Research Directions

et al. 2019

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It is well established that different types of exercise can provide a powerful stimulus for mitochondrial biogenesis. However, there are conflicting findings in the literature, and a consensus has not been reached regarding the efficacy of high-intensity exercise to promote mitochondrial biogenesis in humans. The purpose of this review is to examine current controversies in the field and to highlight some important methodological issues that need to be addressed to resolve existing conflicts.

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“…Schematic of how stable isotope tracers are used to measure protein turnover within a mammalian system highlighting: ( A ) Arterial‐Venous balance techniques and ( B ) FSR techniques (Reprinted with permission from Atherton et al, (Copyright 2015, Elsevier)).…”

Section: Introduction: What Is a Stable Isotope Tracer?mentioning

confidence: 99%

Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism

Wilkinson

2016

Mass Spectrometry Reviews

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Over a century ago, Frederick Soddy provided the first evidence for the existence of isotopes; elements that occupy the same position in the periodic table are essentially chemically identical but differ in mass due to a different number of neutrons within the atomic nucleus. Allied to the discovery of isotopes was the development of some of the first forms of mass spectrometers, driven forward by the Nobel laureates JJ Thomson and FW Aston, enabling the accurate separation, identification, and quantification of the relative abundance of these isotopes. As a result, within a few years, the number of known isotopes both stable and radioactive had greatly increased and there are now over 300 stable or radioisotopes presently known. Unknown at the time, however, was the potential utility of these isotopes within biological disciplines, it was soon discovered that these stable isotopes, particularly those of carbon (13C), nitrogen (15N), oxygen (18O), and hydrogen (2H) could be chemically introduced into organic compounds, such as fatty acids, amino acids, and sugars, and used to “trace” the metabolic fate of these compounds within biological systems. From this important breakthrough, the age of the isotope tracer was born. Over the following 80 yrs, stable isotopes would become a vital tool in not only the biological sciences, but also areas as diverse as forensics, geology, and art. This progress has been almost exclusively driven through the development of new and innovative mass spectrometry equipment from IRMS to GC‐MS to LC‐MS, which has allowed for the accurate quantitation of isotopic abundance within samples of complex matrices. This historical review details the development of stable isotope tracers as metabolic tools, with particular reference to their use in monitoring protein metabolism, highlighting the unique array of tools that are now available for the investigation of protein metabolism in vivo at a whole body down to a single protein level. Importantly, it will detail how this development has been closely aligned to the technological development within the area of mass spectrometry. Without the dedicated development provided by these mass spectrometrists over the past century, the use of stable isotope tracers within the field of protein metabolism would not be as widely applied as it is today, this relationship will no doubt continue to flourish in the future and stable isotope tracers will maintain their importance as a tool within the biological sciences for many years to come. © 2016 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Mass Spec Rev

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Exercise and Regulation of Protein Metabolism

Cited by 24 publications

References 118 publications

Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis

High-Intensity Exercise and Mitochondrial Biogenesis: Current Controversies and Future Research Directions

Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism

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