Funded in part by ZOLL Medical Corporation
Modelling in vivo creatine/phosphocreatine in vitro reveals divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise
Ydfors M, Hughes MC, Laham R, Schlattner U, Norrbom J, Perry CG
The Journal of physiology · 45 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Industry funded
- Company
- ZOLL Medical Corporation
- University or hospital
- York University
- University or hospital
- University College Dublin
- Government
- Canadian Institutes of Health Research
- Government
- CIHR
Based on 5 listed funder(s).
Publication
- Published
- 2015-12-03 · J Physiol · vol. 594 · issue 11 · pp. 3127–3140
- Publisher
- Wiley
- Cited
- 56 citations · more than 96% of similar papers · 7.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 63 works
- Access
- Open access (repository copy)
- Research areas
- Cardiovascular and exercise physiology · Muscle metabolism and nutrition · Adipose Tissue and Metabolism
- Keywords
- Phosphocreatine, Creatine, In vivo, Respiratory system, Human muscle, In vitro, Mitochondrion, Fast twitch muscle, Biology, Internal medicine, Medicine, Skeletal muscle, Cell biology, Energy metabolism, Biochemistry
- MeSH
- muscle, skeletal, mitochondria, humans, creatine, phosphocreatine, adenosine diphosphate, exercise, adaptation, physiological, time factors, adult, male, creatine kinase, mitochondrial form, young adult
6 authors
From SE, CA, FR
- Mia YdforsKarolinska Institutet
- Meghan C. HughesYork University
- Robert LahamYork University
- Uwe SchlattnerLaboratory of Fundamental and Applied Bioenergetics; Université Grenoble Alpes
- Jessica NorrbomKarolinska Institutet
- Christopher G. R. Perry · correspondingYork University
Abstract
Key points
Mitochondrial respiratory sensitivity to ADP is thought to influence muscle fitness and is partly regulated by cytosolic-mitochondrial diffusion of ADP or phosphate shuttling via creatine/phosphocreatine (Cr/PCr) through mitochondrial creatine kinase (mtCK). Previous measurements of respiration in vitro with Cr (saturate mtCK) or without (ADP/ATP diffusion) show mixed responses of ADP sensitivity following acute exercise vs. less sensitivity after chronic exercise. In human muscle, modelling in vivo 'exercising' [Cr:PCr] during in vitro assessments revealed novel responses to exercise that differ from detections with or without Cr (±Cr). Acute exercise increased ADP sensitivity when measured without Cr but had no effect ±Cr or with +Cr:PCr, whereas chronic exercise increased sensitivity ±Cr but lowered sensitivity with +Cr:PCr despite increased markers of mitochondrial oxidative capacity. Controlling in vivo conditions during in vitro respiratory assessments reveals responses to exercise that differ from typical ±Cr comparisons and challenges our understanding of how exercise improves metabolic control in human muscle.
Abstract
Mitochondrial respiratory control by ADP (Kmapp ) is viewed as a critical regulator of muscle energy homeostasis. However, acute exercise increases, decreases or has no effect on Kmapp in human muscle, whereas chronic exercise surprisingly decreases sensitivity despite greater mitochondrial content. We hypothesized that modelling in vivo mitochondrial creatine kinase (mtCK)-dependent phosphate-shuttling conditions in vitro would reveal increased sensitivity (lower Kmapp ) after acute and chronic exercise. The Kmapp was determined in vitro with 20 mm Cr (+Cr), 0 mm Cr (-Cr) or 'in vivo exercising' 20 mm Cr/2.4 mm PCr (Cr:PCr) on vastus lateralis biopsies sampled from 11 men before, immediately after and 3 h after exercise on the first, fifth and ninth sessions over 3 weeks. Dynamic responses to acute exercise occurred throughout training, whereby the first session did not change Kmapp with in vivo Cr:PCr despite increases in -Cr. The fifth session decreased sensitivity with Cr:PCr or +Cr despite no change in -Cr. Chronic exercise increased sensitivity ±Cr in association with increased electron transport chain content (+33-62% complexes I-V), supporting classic proposals that link increased sensitivity to oxidative capacity. However, in vivo Cr:PCr reveals a perplexing decreased sensitivity, contrasting the increases seen ±Cr. Functional responses occurred without changes in fibre type or proteins regulating mitochondrial-cytosolic energy exchange (mtCK, VDAC and ANT). Despite the dynamic responses seen with ±Cr, modelling in vivo phosphate-shuttling conditions in vitro reveals that ADP sensitivity is unchanged after high-intensity exercise and is decreased after training. These findings challenge our understanding of how exercise regulates skeletal muscle energy homeostasis.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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