Activity-dependent bigenomic transcriptional regulation of cytochrome c oxidase in neurons

Abstract

Cytochrome c oxidase, a sensitive indicator of neuronal metabolic capacity and activity, is one of only four proteins in mammalian cells that are bigenomically encoded. The mitochondrial and nuclear genomes have to coordinate to form a functional holoenzyme with 13 subunits. Nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2) are viable candidates for such bigenomic coordination, most likely in association with coactivators, such as peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α). These three factors are themselves regulated by neuronal activity.