Ydfors 2015 J Physiol

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Ydfors M, Hughes MC, Laham R, Schlattner U, Norrbom J, Perry CG (2015) Modelling in vivo creatine/phosphocreatine in vitro reveal divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise. J Physiol 594:3127-40.

» PMID: 26631938

Ydfors M, Hughes MC, Laham R, Schlattner U, Norrbom J, Perry CG (2015) J Physiol

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 modelling in vivo mitochondrial creatine kinase (mtCK)-dependent phosphate shuttling conditions in vitro would reveal increased sensitivity (lower Kmapp) following acute and chronic exercise. 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 males before, immediately Post and 3hr Post exercise on the 1st, 5th and 9th sessions over 3 weeks. Dynamic responses to acute exercise occurred throughout training, whereby the 1st session did not change Kmapp with in vivo Cr:PCr despite increases in -Cr. The 5th 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 linking 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, ANT). Despite the dynamic responses seen with +/- Cr, modelling in vivo phosphate shuttling conditions in vitro reveals ADP sensitivity is unchanged following high intensity exercise and is decreased after training. These findings challenge our understanding of how exercise regulates skeletal muscle energy homeostasis.

Keywords: Blebbistatin

O2k-Network Lab: FR Grenoble Saks VA, FR Grenoble Schlattner U, CA Guelph Holloway GP, CA Toronto Perry CG, US NC Greenville Neufer PD


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style 


Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase  Regulation: ADP, PCr;Cr  Coupling state: OXPHOS  Pathway:HRR: Oxygraph-2k 

2016-01