Transcriptional and post-transcriptional regulation of mitochondrial biogenesis in skeletal muscle: effects of exercise and aging.
Acute contractile activity of skeletal muscle initiates the activation of signaling kinases. This promotes the phosphorylation of transcription factors, leading to enhanced DNA binding and transcriptional activation and/or repression. The mRNA products of nuclear genes encoding mitochondrial proteins are translated in the cytosol and imported into pre-existing mitochondria. When contractile activity is repeated, the recapitulation of these cellular events progressively leads to an expansion of the mitochondrial reticulum within muscle. This has physiologically relevant health benefit, including enhanced lipid metabolism and reduced muscle fatigability. In aging skeletal muscle, the response to contractile activity appears to be attenuated, suggesting that a greater contractile stimulus is required to attain a similar phenotype adaptation. This review summarizes our current understanding of the effects of exercise on the gene expression pathway leading to organelle biogenesis in muscle.
Ljubicic
Vladimir
V
School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M3J 1P3.
Joseph
Anna-Maria
AM
Saleem
Ayesha
A
Uguccioni
Giulia
G
Collu-Marchese
Melania
M
Lai
Ruanne Y J
RY
Nguyen
Linda M-D
LM
Hood
David A
DA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000254:growth & development / Q000502:physiology*; D001678:Organelle Biogenesis; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D002118:Calcium