Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work

Desplanches, Dominique; Amami, Myriam; Dupré-Aucouturier, Sylvie; Valdivieso, Paola; Schmutz, Silvia; Müeller, Matthias; Hoppeler, Hans; Kreis, Roland; Flück, Martin

doi:10.1007/s00421-013-2783-8

Cited by 36 publications

(47 citation statements)

References 47 publications

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“…Endurance exercise training in rats leads to an increase of myoglobin in the trained muscles (Pattengale and Holloszy, 1967). In humans, normoxic endurance training has no effect on muscle myoglobin content (Masuda et al, 2001); to increase myoglobin concentration in human muscle an additional hypoxic stimulus is necessary (Desplanches et al, 2014). In humans, mitochondrial content in the vastus lateralis muscle and endurance capacity are completely unaffected by 4 weeks of a high fat diet (Vogt et al, 2003).…”

Section: Summary and Comparative Perspective Of Muscle Plasticitymentioning

confidence: 99%

Molecular networks in skeletal muscle plasticity

Hoppeler

2016

Journal of Experimental Biology

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168

117

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The skeletal muscle phenotype is subject to considerable malleability depending on use as well as internal and external cues. In humans, low-load endurance-type exercise leads to qualitative changes of muscle tissue characterized by an increase in structures supporting oxygen delivery and consumption, such as capillaries and mitochondria. High-load strength-type exercise leads to growth of muscle fibers dominated by an increase in contractile proteins. In endurance exercise, stress-induced signaling leads to transcriptional upregulation of genes, with Ca 2+ signaling and the energy status of the muscle cells sensed through AMPK being major input determinants. Several interrelated signaling pathways converge on the transcriptional co-activator PGC-1α, perceived to be the coordinator of much of the transcriptional and post-transcriptional processes. Strength training is dominated by a translational upregulation controlled by mTORC1. mTORC1 is mainly regulated by an insulin-and/or growth-factor-dependent signaling cascade as well as mechanical and nutritional cues. Muscle growth is further supported by DNA recruitment through activation and incorporation of satellite cells. In addition, there are several negative regulators of muscle mass. We currently have a good descriptive understanding of the molecular mechanisms controlling the muscle phenotype. The topology of signaling networks seems highly conserved among species, with the signaling outcome being dependent on the particular way individual species make use of the options offered by the multi-nodal networks. As a consequence, muscle structural and functional modifications can be achieved by an almost unlimited combination of inputs and downstream signaling events.

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Section: Summary and Comparative Perspective Of Muscle Plasticitymentioning

confidence: 99%

Molecular networks in skeletal muscle plasticity

Hoppeler

2016

Journal of Experimental Biology

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168

117

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“…), and may only become upregulated when exercise training is imposed on top of the hypoxic stimulus (Hoppeler & Vogt, ; Desplanches et al . ). Moreover, in one study muscle levels of myoglobin fell by 35% in human subjects after 7–9 days at 4559 m, alongside the downregulation of other iron‐related proteins and loss of total muscle iron content – effects that were attributed to the need to mobilise intramuscular iron to support the erythropoietic response (Robach et al .…”

Section: Introductionmentioning

confidence: 97%

Mitochondrial function at extreme high altitude

Murray

Horscroft

2015

The Journal of Physiology

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At high altitude, barometric pressure falls and with it inspired P O 2 , potentially compromising O 2 delivery to the tissues. With sufficient acclimatisation, the erythropoietic response increases red cell mass such that arterial O 2 content (C aO 2 ) is restored; however arterial P O 2 (P aO 2 ) remains low, and the diffusion of O 2 from capillary to mitochondrion is impaired. Mitochondrial respiration and aerobic capacity are thus limited, whilst reactive oxygen species (ROS) production increases. Restoration of P aO 2 with supplementary O 2 does not fully restore aerobic capacity in acclimatised individuals, possibly indicating a peripheral impairment. With prolonged exposure to extreme high altitude (>5500 m), muscle mitochondrial volume density falls, with a particular loss of the subsarcolemmal population. It is not clear whether this represents acclimatisation or deterioration, but it does appear to be regulated, with levels of the mitochondrial biogenesis factor PGC-1α falling, and shows similarities to adapted Tibetan highlanders. Qualitative changes in mitochondrial function also occur, and do so at more moderate high altitudes with shorter periods of exposure. Electron transport chain complexes are downregulated, possibly mitigating the increase in ROS production. Fatty acid oxidation capacity is decreased and there may be improvements in biochemical coupling at the mitochondrial inner membrane that enhance O 2 efficiency. Creatine kinase expression falls, possibly impairing high-energy phosphate transfer from the mitochondria to myofibrils. In climbers returning from the summit of Everest, cardiac energetic reserve (phosphocreatine/ATP) falls, but skeletal muscle energetics are well preserved, possibly supporting the notion that mitochondrial remodelling is a core feature of acclimatisation to extreme high altitude. Abbreviations31 P-MRS, 31 P magnetic resonance spectroscopy; BNIP3, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; ETC, electron transport chain; HIF, hypoxia-inducible factor; HOAD, 3-hydroxyacyl-CoA dehydrogenase; PGC, peroxisome proliferator-activated receptor gamma co-activator; P O2 , partial pressure of O 2 ; PCr, phosphocreatine; PPARα, peroxisome proliferator-activated receptor alpha; ROS, reactive oxygen species; UCP3, uncoupling protein 3; V max , maximum rate of mitochondrial oxygen consumption; V O2 max , maximum rate of whole-body oxygen consumption.

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“…In support of this theory, living near sea level but training in hypoxic conditions, effectively increased mitochondrial volume density (Mito VD ) more than the complementary live low–train low (LLTL) training (Desplanches et al . , ; Vogt et al . ; Schmutz et al .…”

Section: Introductionmentioning

confidence: 99%

Twenty‐eight days of exposure to 3454 m increases mitochondrial volume density in human skeletal muscle

Jacobs

Lundby

Fenk

et al. 2015

The Journal of Physiology

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Key pointsr It is generally accepted that mitochondrial volume density in human skeletal muscle diminishes with chronic high altitude exposure.r All data supporting this concept were collected during mountaineering expeditions, which are associated with the confounding effects of whole body negative energy balance.r Here we examine the effect of 28 days of exposure to 3454 m on skeletal muscle mitochondrial volume density in a setting where whole body weight, whole body composition, leg lean mass, skeletal muscle fibre area and maximal power output were preserved.r Our results demonstrate that total skeletal muscle mitochondrial volume density increases in response to high altitude exposure secondary to a preferential increase in intermyofibrillar mitochondrial populations.r This study provides direct evidence contradicting the notion that high altitude exposure diminishes skeletal muscle mitochondrial volume density, highlighting an inconsistent understanding of the role of hypoxia on skeletal muscle mitochondria.Abstract The role of hypoxia on skeletal muscle mitochondria is controversial. Studies superimposing exercise training on hypoxic exposure demonstrate an increase in skeletal muscle mitochondrial volume density (Mito VD ) over equivalent normoxic training. In contrast, reductions in both skeletal muscle mass and Mito VD have been reported following mountaineering expeditions. These observations may, however, be confounded by negative energy balance, which may obscure the results. Accordingly we sought to examine the effects of high altitude hypoxic exposure on mitochondrial characteristics, with emphasis on Mito VD , while minimizing changes in energy balance. For this purpose, skeletal muscle biopsies were obtained from nine lowlanders at sea level (Pre) and following 7 and 28 days of exposure to 3454 m. Maximal ergometer power output, whole body weight and composition, leg lean mass and skeletal muscle fibre area all remained unchanged following the altitude exposure. Transmission electron microscopy determined that intermyofibrillar (IMF) Mito VD was augmented (P = 0.028) by 11.5 ± 9.2% from Pre (5.05 ± 0.9%) to 28 Days (5.61 ± 0.04%). In contrast, there was no change in subsarcolemmal (SS) Mito VD . As a result, total Mito VD (IMF + SS) was increased (P = 0.031) from 6.20 ± 1.5% at Pre to 6.62 ± 1.4% at 28 Days (7.8 ± 9.3%). At the same time no changes in mass-specific respiratory capacities, mitochondrial protein or antioxidant content were found. This study demonstrates that skeletal muscle Mito VD may increase with 28 days acclimation to 3454 m.

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Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work

Cited by 36 publications

References 47 publications

Molecular networks in skeletal muscle plasticity

Molecular networks in skeletal muscle plasticity

Mitochondrial function at extreme high altitude

Twenty‐eight days of exposure to 3454 m increases mitochondrial volume density in human skeletal muscle

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