Transcriptional regulatory circuits controlling mitochondrial biogenesis and function

Over the past decade, significant new insight has been gained into the circuitry of molecular regulatory cascades controlling mitochondrial biogenesis and function (Fig. 3). The interdependence of nuclear and mitochondrial genomes has evolved with the emergence of the mitochondrion as a eukaryotic organelle. It is likely that the complexity of the mammalian organism mandates a complex regulatory network that provides for the dynamic coordinate control of nuclear and mitochondrial genes during development and in the adult. This regulatory circuitry not only triggers mitochondrial biogenesis in response to developmental and physiologic cues, but also confers cell- and tissue-specific features. New insight into the dynamic control of mitochondrial function and biogenesis has been provided by the identification of relevant transcription factors, transcriptional coactivators, and upstream signaling events. However, the mechanisms involved in the control of cell-specific mitochondrial phenotypes and the full cast of transcriptional regulatory factors comprise an exciting investigative frontier. New experimental approaches such as the delineation of tissue-specific mitochondrial proteomes (Mootha et al. 2003) should provide an excellent framework for future studies aimed at understanding the molecular events involved in defining the mitochondrial phenotype.