Mitochondria are remarkable organelles that dynamically remodel during cellular differentiation and in response to external stimuli. They are found in virtually all tissues, though their protein composition and enzymatic activities vary across cell types. Widely recognized as the center-stage for oxidative phosphorylation (OXPHOS), mitochondria also host other pathways, including the TCA cycle, pyrimidine biosynthesis, heme and urea metabolism, and fatty acid oxidation. In addition, this organelle contributes to cellular ion and ROS homeostasis, and can couple the metabolic state to programmed cell death.

A long-term goal of our group is to develop predictive models of mitochondrial function that combine genome-scale expression profiles with biochemical physiology. Such models may help us to better understand the basic biology of this organelle and its ability to adapt at a broad range of time-scales.

An important first step towards this goal is the compilation of a comprehensive parts-list for this organelle. At present only ~750 of the estimated 1500 human mitochondrial proteins have been identified. Our group is using a combination of tandem mass spectrometry and computational genomics to systematically expand this inventory. We are also cataloging the tissue-specific differences in mitochondrial protein composition.

We have begun to monitor the activity of these genes under basal and perturbed states to gain insights into their function. Such studies also enable us to systematically characterize the transcriptional mechanisms that ensure state-specific mitochondrial biogenesis. We employ complementary profiling strategies, in combination with computational and comparative genomics, to achieve these goals.