PGC-1alpha activation as a therapeutic approach in mitochondrial disease.

Mitochondria play a central role in cellular homeostasis. Hence, mitochondrial dysfunction resulting in impaired ATP supply is detrimental to cell viability and causes severe and often fatal disorders. Current treatment of these mitochondrial disorders is limited and mostly addresses the symptoms, but not the deficiency itself. Recent work in cell and animal models of mitochondrial disease shows that increased mitochondrial biogenesis can boost residual OXPHOS capacity and thereby prevent the bioenergetic crisis. In animal models, this strategy results in increased health and lifespan. Here, I review which mitochondrial processes are affected in known mitochondrial disorders and discuss why PGC-1alpha mediated mitochondrial biogenesis offers a promising venue for treatment of mitochondrial disorders.