The respiratory chain in the mitochondrial inner membrane is the "machine" that captures energy for the cell when food is oxidized. It is built from proteins encoded in both the nucleus and a small chromosome inside mitochondria. We are trying to understand the mechanisms that control mitochondrial gene expression and target its protein products to the assembly of the respiratory chain.

This work is prompted by an interest in basic cellular mechanisms.

We have identified mechanisms that control gene expression at the level of translation and couple expression to membrane insertion and respiratory complex assembly. The results of our work have been disseminated through peer-reviewed publication, seminars at sister institutions, and presentations at national and international meetings of scientists.

Our detailed examination of mitochondrial gene expression in yeast has revealed that organellar gene regulation often takes place at the level of protein synthesis instead of mRNA synthesis. And it has revealed that this regulatory mechanism plays an important role in targeting the newly synthesized mitochondrial gene products to sites where they can be efficiently assembled into respiratory complexes. More recently we have explored mechanisms by which the rate of assembly of a respiratory chain complex may feedback-control the rate of synthesis of one of its key components. These studies have taken advantage of the remarkably powerful genetic approaches that can be used to study yeast, principally the replacement of genes in both nuclear and mitochondrial chromosomes but not in more complex organisms, such as plants and animals. Thus our exploratory work has provided a trailblazing look at the questions that should be studied in these more complex organisms and is helping to elucidate basic mechanisms and potential drug targets in fungi.

Basic biological research on cellular mechanisms

National Institute of General Medical Sciences (NIH)