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Schlagowski 2014 J Appl Physiol

From Bioblast
Publications in the MiPMap
Schlagowski AI, Singh F, Charles AL, Gali Ramamoorthy T, Favret F, Piquard F, Geny B, Zoll J (2014) Mitochondrial uncoupling reduces exercise capacity despite several skeletal muscle metabolic adaptations. J Appl Physiol 116:364-75.

» PMID: 24336883

Schlagowski AI, Singh F, Charles AL, Gali Ramamoorthy T, Favret F, Piquard F, Geny Bernard, Zoll J (2014) J Appl Physiol

Abstract: The effects of mitochondrial uncoupling on skeletal muscle mitochondrial adaptation and maximal exercise capacity are unknown. In this study, rats were divided into a control group (CTL, n = 8) and a group treated with 2,4-dinitrophenol, a mitochondrial uncoupler, for 28 days (DNP, 30 mg·kg(-1)·day(-1) in drinking water, n = 8). The DNP group had a significantly lower body mass (P < 0.05) and a higher resting oxygen uptake (Vo2, P < 0.005). The incremental treadmill test showed that maximal running speed and running economy (P < 0.01) were impaired but that maximal Vo2 (Vo2max) was higher in the DNP-treated rats (P < 0.05). In skinned gastrocnemius fibers, basal respiration (V0) was higher (P < 0.01) in the DNP-treated animals, whereas the acceptor control ratio (ACR, Vmax/V0) was significantly lower (P < 0.05), indicating a reduction in OXPHOS efficiency. In skeletal muscle, DNP activated the mitochondrial biogenesis pathway, as indicated by changes in the mRNA expression of PGC1-α and -β, NRF-1 and -2, and TFAM, and increased the mRNA expression of cytochrome oxidase 1 (P < 0.01). The expression of two mitochondrial proteins (prohibitin and Ndufs 3) was higher after DNP treatment. Mitochondrial fission 1 protein (Fis-1) was increased in the DNP group (P < 0.01), but mitofusin-1 and -2 were unchanged. Histochemical staining for NADH dehydrogenase and succinate dehydrogenase activity in the gastrocnemius muscle revealed an increase in the proportion of oxidative fibers after DNP treatment. Our study shows that mitochondrial uncoupling induces several skeletal muscle adaptations, highlighting the role of mitochondrial coupling as a critical factor for maximal exercise capacities. These results emphasize the importance of investigating the qualitative aspects of mitochondrial function in addition to the amount of mitochondria. Keywords: 2, 4-dinitrophenol, Mitochondrial uncoupling, Exhaustive exercise Maximal running speed, Gas exchanges, Maximal oxygen uptake

O2k-Network Lab: FR Strasbourg Zoll J


Labels: MiParea: Respiration 

Stress:Mitochondrial disease  Organism: Rat  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS  Pathway: NS  HRR: Oxygraph-2k