In cells from patients suffering from mitochondrial myopathy and carrying the m.3243A>G mutation in the MT-TL1 mitochondrial gene, in which the PI3K-AKT-MTORC1 signalling pathway is abnormally activated, researchers looked at the effects of inhibiting this signalling pathway (with rapamycin, LY294002, etc.) and showed :
- restoration of mitophagy and a reduction in mutational load ;
- signs of improvement in mitochondrial function: increase in mitochondrial membrane potential, improved oxidative phosphorylation, improvement in mitochondrial function preceding the reduction in mutational load.
These results indicate that the PI3K-AKT-MTORC1 pathway plays a role in mitochondrial metabolism and that oxidative phosphorylation is essential for the activation of mitophagy, the presence of pathogenic mitochondrial DNA alone not being sufficient to trigger selection against mutation by mitophagy.
