Mitochondria produce most of the cellular ATP by the process of oxidative phosphorylation (OXPHOS) and generate most of the endogenous oxygen radicals as a toxic by-product. In addition, mitochondria are central in the regulation of apoptosis, calcium homeostasis and cytoplasmic redox state. The 16-kb mitochondrial genome encodes only 13 of the more than 100 proteins involved in OXPHOS. Most mitochondrial proteins are encoded by the nuclear genome. Although the role of mitochondria in various cellular processes is becoming more and more apparent, little is known about the regulation of mitochondria-related gene expression. We have begun to use DNA microarray technologies to both identify genes related to mitochondrial function as well as characterize changes in mitochondrial gene expression during development and mitochondrial dysfunction. Working in the mouse system, we have chosen a preliminary set of 300 genes that are related to various aspects of mitochondrial function. Using a standard two-colour fluorescent system, we are analysing the temporal regulation of mitochondrial gene expression during early development. Experiments are also underway to analyse the changes in gene expression caused by genetic models of mitochondrial dysfunction. Through these experiments, we hope to better understand the complex interaction between nuclear and mitochondrial DNA gene expression in mitochondrial biogenesis and bioenergetics.