The Role of PGC-1α-Mediated Mitochondrial Biogenesis in Neurons.

ABSTRACT

Neurons are highly dependent on mitochondrial ATP production and Ca2+ buffering. Neurons have unique compartmentalized anatomy and energy requirements, and each compartment requires continuously renewed mitochondria to maintain neuronal survival and activity. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a key factor in the regulation of mitochondrial biogenesis. It is widely accepted that mitochondria are synthesized in the cell body and transported via axons to the distal end. However, axonal mitochondrial biogenesis is necessary to maintain axonal bioenergy supply and mitochondrial density due to limitations in mitochondrial axonal transport rate and mitochondrial protein lifespan. In addition, impaired mitochondrial biogenesis leading to inadequate energy supply and neuronal damage has been observed in neurological disorders. In this review, we focus on the sites where mitochondrial biogenesis occurs in neurons and the mechanisms by which it maintains axonal mitochondrial density. Finally, we summarize several neurological disorders in which mitochondrial biogenesis is affected.