Project 1: The biogenesis of fully functional mitochondria involves the expression of both nuclear and mitochondrial genes. While the contribution of the mitochondrial genome is important for the function of the oxidative phosphorylation system, the vast majority of mitochondrial proteins are encoded by the nucleus and translated on cytosolic ribosomes. To reach their destination, these proteins must be correctly targeted to mitochondria and sorted to the correct mitochondrial subcompartment. We are investigating the structure and function of the proteins in a complex found on the outer surface of the mitochondrial outer membrane that is responsible for the import of proteins into mitochondria. This complex recognizes proteins specifically destined for the mitochondria and initiates the process of importing them into the organelle. My laboratory utilizes genetics, molecular biology, and biochemistry to investigate the mechanisms by which this is achieved.
Project 2: When the oxidative phosphorylation system of mitochondria is impaired by inhibitors or mutations affecting the process, the compromised mitochondria send signals to the nucleus which affect the regulation of several nuclear genes. The nature of these signals and the pathway by which they are transmitted are completely unknown. We are investigating the process by studying the regulation of the alternative oxidase of Neurospora crassa. This enzyme is only synthesized in strains that have inefficient oxidative phosphorylation. Preliminary results suggest that a signal transduction pathway beginning in the functionally compromised mitochondria induces the transcription of the alternative oxidase. We are attempting to elucidate the components of the pathway using genetic and molecular biological techniques.