Activity-dependent regulation of nuclear respiratory factor-1, nuclear respiratory factor-2, and peroxisome proliferator-activated receptor gamma coactivator-1 in neurons.

Nuclear respiratory factor-1 and nuclear respiratory factor-2 activate the transcription of several respiratory chain enzymes and are prime candidates for bigenomic coordinated regulation of cytochrome oxidase subunit genes from the two genomes. Peroxisome proliferator-activated receptor gamma coactivator 1 is a proposed coactivator of nuclear respiratory factor-1 and nuclear respiratory factor-2-dependent transcription, but its significance and function in neurons are unknown. Our current study indicates that nuclear respiratory factor-1, nuclear respiratory factor-2, and peroxisome proliferator-activated receptor gamma coactivator-1 are expressed in rat visual cortical neurons, and that neuronal activity directly regulates the protein and mRNA expressions of these factors after functional inactivation in vivo and in vitro. Changes in peroxisome proliferator-activated receptor gamma coactivator-1 preceded those of nuclear respiratory factor-1 and nuclear respiratory factor-2, suggesting that it may be the prime sensor of neuronal activity and its energy demand.