Control of gene expression and mitochondrial biogenesis in the muscular adaptation to endurance exercise.
Every time a bout of exercise is performed, a change in gene expression occurs within the contracting muscle. Over the course of many repeated bouts of exercise (i.e. training), the cumulative effects of these alterations lead to a change in muscle phenotype. One of the most prominent of these adaptations is an increase in mitochondrial content, which confers a greater resistance to muscle fatigue. This essay reviews current knowledge on the regulation of exercise-induced mitochondrial biogenesis at the molecular level. The major steps involved include, (i) transcriptional regulation of nuclear-encoded genes encoding mitochondrial proteins by the coactivator peroxisome-proliferator-activated receptor g coactivator-1, (ii) control of mitochondrial DNA gene expression by the transcription factor Tfam, (iii) mitochondrial fission and fusion mechanisms, and (iv) import of nuclear-derived gene products into the mitochondrion via the protein import machinery. It is now known that exercise can modify the rates of several of these steps, leading to mitochondrial biogenesis. An understanding of how exercise can produce this effect could help us decide whether exercise is beneficial for patients suffering from mitochondrial disorders, as well as a variety of metabolic diseases.
Joseph
Anna-Maria
AM
Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3.
Pilegaard
Henriette
H
Litvintsev
Anastassia
A
Leick
Lotte
L
Hood
David A
DA
D000222:Adaptation, Physiological; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008931:Mitochondria, Muscle / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010807:Physical Endurance / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology; D021381:Protein Transport; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D004272:DNA, Mitochondrial; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors