Research program title
Linking peroxide sensing and heme mobilization
Cells must rapidly detect and tightly control reactive oxygen species to prevent oxidative stress. We are exploring how this is achieved using yeast as a model eukaryotic cell. For example, most hydrogen peroxide is generated during mitochondrial respiration and we have discovered a novel mechanism of peroxide sensing in these organelles. The sensor we identified is Ccp1 (cytochrome c peroxidase), a heme protein that rapidly reacts with peroxide. This is the first example of heme-based peroxide signaling since established mechanisms are dominated by thiol-based sensors. Surprisingly, we find that high peroxide levels mobilize Ccp1’s heme, which is recruited for the maturation of catalase, a highly efficient enzyme in peroxide removal. Our observations link, for the first time, peroxide sensing with heme mobilization, which has far-reaching implications for coordination of the stress response in cells. To understand how peroxide mobilizes Ccp1’s heme and contributes to antioxidant defense, we are performing high-performance mass spectrometric analysis of Ccp1 and key variants isolated from respiring cells. The Ccp1 variants also will be fused to green fluorescent protein (GFP) to monitor their heme loading and location in cells using fluorescence-lifetime imaging microscopy (FLIM). Linking antioxidant stress and heme mobilization is of particular importance in biology since numerous heme proteins are involved in reactions that generate or consume reactive oxygen species.
Academic qualifications required
PhD in Chemistry, Biochemistry, or Biology with experience in biophysical studies on proteins; experience in protein mass spectrometry would be a major asset.