Plasticity of skeletal muscle mitochondria: structure and function.
Mitochondria in skeletal muscle tissue can undergo rapid and characteristic changes as a consequence of manipulations of muscle use and environmental conditions. Endurance exercise training leads to increases of mitochondrial volume of up to 50% in training interventions of a few weeks in previously untrained subjects. Additionally, a shift of substrate metabolism toward a higher reliance on lipids is observed, structurally reflected as a doubling of the intramyocellular lipid content. A similar increase in intramyocellular lipids without an increase in mitochondrial volume is observed as a consequence of a high-fat diet. Strength training has a major impact on muscle myofibrillar volume, however the mitochondrial compartment appears relatively unchanged. Bedrest and microgravity conditions lead to losses of both myofibrillar and mitochondrial volume, likely as a consequence of the decrease in metabolic and mechanical stress on muscle tissue. Permanent severe hypoxia leads to a loss of muscle mass and muscle oxidative capacity; however, hypoxia signaling events are triggered, which lead to distinct reprogramming phenomena of the transcriptome of the muscle cells. The molecular mechanisms that orchestrate the plasticity of skeletal muscle mitochondria are just beginning to unfold. The present data indicate that transcriptional events largely contribute to increases in mitochondrial mass in human skeletal muscle with endurance training. Expression of mitochondrial proteins from the nuclear and mitochondrial genomes is coordinated and involves the nuclear-encoded transcription factors NRF-1 and TFAM. Transcription of genes encoding the mitochondrial proteins involved in beta oxidation can be regulated separately from the genes of the Krebs cycle and the respiratory chain. Transcription factors AP-1 and PPARalpha/gamma and the protein kinase AMPK are signaling molecules that transduce the metabolic and mechanical factors sensed during endurance training into the complex transcriptional adaptations of mitochondrial proteins.
Hoppeler
Hans
H
Department of Anatomy, University of Bern, Switzerland. hoppeler@ana.unibe.ch
Fluck
Martin
M
D000222:Adaptation, Physiological; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D010807:Physical Endurance / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D014893:Weightlessness
D024101:Mitochondrial Proteins; D011494:Protein Kinases