Figure 7. A positive regulatory loop between mitochondrial activity and nuclear genes such as PGC-1α and PPARδ could be able to coordinate the increase in oxidative metabolism and the expression of slower myosin isoforms.

A stimulation of mitochondrial activity induced by p43, could modulate Ca²⁺ signalling and mitochondrial reactive oxygen species production, which are well known for altering the activity of some transcriptional factors such as NFκB and AP-1. In this way mitochondrial activity could affect nuclear gene expression of proteins such as PGC-1α and PPARδ which are involved in muscle specification and in the regulation of mitochondrial biogenesis. This positive regulatory loop could be deeply involved in the determination of muscle metabolic and contractile phenotypes.