Biology subjects

Stocks, B.

Publications and source records attributed to Stocks, B..

3 recordsLinked to original sources

bioRxiv2021

High-Intensity Interval Training Remodels the Proteome and Acetylome of Human Skeletal Muscle

Exercise is an effective strategy in the prevention and treatment of metabolic diseases. Alterations in the skeletal muscle proteome, including post-translational modifications, regulate its metabolic adaptations to exercise. Here, we examined the effect of high-intensity interval training (HIIT) on the proteome and acetylome of human skeletal muscle, revealing the response of 3168 proteins and 1263 lysine acetyl-sites on 464 acetylated proteins. We identified global protein adaptations to exercise training involved in metabolism, excitation-contraction coupling, and myofibrillar calcium sensitivity. Furthermore, HIIT increased the acetylation of mitochondrial proteins, particularly those of complex V. We also highlight the regulation of exercise-responsive histone acetyl-sites. These data demonstrate the plasticity of the skeletal muscle proteome and acetylome, providing insight into the regulation of contractile, metabolic and transcriptional processes within skeletal muscle. Herein, we provide a substantial hypothesis-generating resource to stimulate further mechanistic research investigating how exercise improves metabolic health. Impact statementHostrup and colleagues identify global proteomic and acetylomic adaptations to high-intensity interval training, demonstrating adaptations to processes regulating metabolism and contraction.

physiology↗

bioRxiv2020

Nicotinamide Riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise

Oral supplementation of the NAD+ precursor Nicotinamide Riboside (NR) has been reported to increase Sirtuin (SIRT) signalling, mitochondrial biogenesis and endurance capacity in rodent skeletal muscle. However, whether NR supplementation can elicit a similar response in human skeletal muscle is unclear. This study aimed to assess the effect of 7-day NR supplementation on exercise-induced transduction and transcriptional responses in skeletal muscle of young, healthy, recreationally active human volunteers. In a double-blinded, randomised, counter-balanced, crossover design, eight male participants (age: 23 ± 4 years, VO2peak: 46.5 ± 4.4 mL·kg-1·min-1) received one week of NR or cellulose placebo (PLA) supplementation (1000 mg·d-1) before performing one hour of cycling at 60% Wmax. Muscle biopsies were collected prior to supplementation and pre-, immediately and three-hours post-exercise from the medial vastus lateralis, whilst venous blood samples were collected throughout the trial. Global acetylation, auto-PARylation of PARP1, acetylation of p53Lys382 and MnSODLys122 were unaffected by NR supplementation or exercise. Exercise led to an increase in AMPKThr172 (1.6-fold), and ACCSer79 (4-fold) phosphorylation, in addition to an increase in PGC-1α (∼5-fold) and PDK4 (∼10-fold) mRNA expression, however NR had no additional effect on this response. There was also no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Finally, NR supplementation blunted the exercise induced activation of skeletal muscle NNMT mRNA expression, but had no effect on mRNA expression of NMRK1, NAMPT or NMNAT1, which were not significantly affected by NR supplementation or exercise. In summary, one week of NR supplementation does not augment skeletal muscle signal transduction pathways implicated in mitochondrial adaptation to endurance exercise.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗

bioRxiv2019

Mass-spectrometry based proteomics reveals mitochondrial supercomplexome plasticity

Mitochondrial respiratory complex subunits assemble in supercomplexes. Studies of supercomplexes have typically relied upon antibody-based protein quantification, often limited to the analysis of a single subunit per respiratory complex. To provide a deeper insight into mitochondrial and supercomplex plasticity, we combined Blue Native Polyacrylamide Gel Electrophoresis (BN-PAGE) and mass spectrometry to determine the supercomplexome of skeletal muscle from sedentary and exercise-trained mice. We quantified 422 mitochondrial proteins within ten supercomplex bands, in which we showed the debated presence of complex II and V. Upon exercise-induced mitochondrial biogenesis, non-stoichiometric changes in subunits and incorporation into supercomplexes was apparent. We uncovered the dynamics of supercomplex-related assembly proteins and mtDNA-encoded subunits within supercomplexes, as well as the complexes of ubiquinone biosynthesis enzymes and Lactb, a mitochondrial-localized protein implicated in obesity. Our approach can be applied to broad biological systems. In this instance, comprehensively analyzing respiratory supercomplexes illuminates previously undetectable complexity in mitochondrial plasticity. HighlightsO_LIComprehensive quantification of respiratory subunits within supercomplexes C_LIO_LIComplex II and V assemble within supercomplexes C_LIO_LIMitochondrial-encoded subunits display elevated upregulation upon exercise training C_LIO_LIExercise increases ubiquinone biosynthesis enzyme complexes C_LI

molecular biology↗