Nuclear respiratory factors and the pathways of nuclear-mitochondrial interaction

Abstract

Mitochondrial oxidative pathways can be adversely affected by mutations in both nuclear and mitochondrial genomes. Recent evidence indicates that cardiac impairment is an important clinical feature of mitochondrial diseases resulting from such mutations. Understanding the regulatory interplay between nuclear and mitochondrial genetic systems may yield new insights into human genetic defects affecting cardiac function. Nuclear respiratory factors (NRF-1 and NRF-2) are transcriptional activators that act on a significant subset of nuclear genes required for mitochondrial respiration. These factors most likely participate in nuclear-mitochondrial interactions by helping to coordinate the synthesis of respiratory chain subunits with components of the mitochondrial transcription, replication, and heme biosynthetic machinery. Thus, NRFs and related factors are likely contributors to the nuclear control of mitochondrial energy production that is essential for normal myocardial function.