Nuclear control of respiratory gene expression in mammalian cells

Abstract

The mitochondrial respiratory apparatus is the product of both nuclear and mitochondrial genes. The protein coding capacity of mtDNA is restricted to the expression of 13 respiratory subunits and thus nuclear genes play a predominant role in the biosynthesis of the respiratory chain and in the expression of the mitochondrial genome. Transcriptional regulators that act on both nuclear and mitochondrial genes have been implicated in the bi-genomic expression of the respiratory chain. Mitochondrial transcription is directed by a small number of nucleus-encoded factors (Tfam, TFB1M, TFB2M, mTERF). The expression of these factors is coordinated with that of nuclear respiratory proteins through the action of transcriptional activators and coactivators. In particular, environmental signals induce the expression of PGC-1 family coactivators (PGC-1alpha, PGC-1beta, and PRC), which in turn target specific transcription factors (NRF-1, NRF-2, and ERR alpha) in the expression of respiratory genes. This system provides a mechanism for linking respiratory chain expression to environmental conditions and for integrating it with other functions related to cellular energetics.