Figure 4. Cellular events proposed to be involved in inducing mitochondrial biogenesis and up-regulation of some metabolic proteins in muscle at rest and during exercise.

1, increases in the [AMP]/[ATP] ratio activates AMPK in exercising muscle and ZMP activates AMPK in resting muscle. 2, AMPK and several other signalling molecules increase transcription of nuclear genes encoding metabolic proteins and transcriptional modulators. 3, transcription modulators subsequently activate nuclear genes encoding various mitochondrial and metabolic enzymes as well as mitochondrial genes. 4, synthesis of mitochondrial and metabolic enzymes as well as transcription factor(s) important for activation of mitochondrial genes in the mitochondrial matrix. 5, formation of new mitochondria.