The mitochondrion is the major energy generating organelle of the cell and the site of other basic processes, including apoptosis. The mitochondrial functions are performed in concert with other cell compartments and are regulated by various extracellular and intracellular signals. Several nuclear receptors and other nuclear transcription factors, such as NF-kappa B, AP-1, CREB and p53, involved in growth, metabolic and developmental processes, have been detected in mitochondria. This finding raises the question as to the role of these regulatory molecules in their "new" environment. Experimental evidence supports the action of the mitochondrially localized transcription factors on mitochondrial transcription, energy yield and apoptosis, extending the known nuclear role of these molecules outside the nucleus. A principle of coordination of nuclear and mitochondrial gene transcription has been ascertained as regards the regulatory action of steroid and thyroid hormones on energy yield. Accordingly, the same nuclear receptors, localized in the two compartments-nuclei and mitochondria-regulate transcription of genes serving a common function by way of interaction with common binding sites in the two genomes. This principle is now expanding to encompass other nuclearly and mitochondrially localized transcription factors.