Description of Research Expertise:
Study of iron metabolism, iron trafficking, mitochondrial function, heme and Fe-S proteins.
Key words: mitochondria, yeast, Fe-S, heme, frataxin, mitochondrial carrier proteins, pyrimidines, ring sideroblast
In most eukaryotes (including yeast and human cells) the essential iron containing cofactors, Fe-S and heme, are made in the mitochondria.
Iron transport across the ion impermeable inner membrane (from cytoplasm into the mitochondrial matrix) is an essential process for cell viability and yet it is poorly characterized. This is surprising but, in fact, calcium transport into mitochondria is only beginning to be understood this year. We have found candidate mitochondrial iron transporters and we are developing assays measuring iron import and iron use in mitochondria. An unanticipated connection to pyrimidine exchange has been discovered and this is a current focus of research. A second object of study is to understand Fe-S cluster biogenesis in mitochondria. Frataxin, a disease gene involved in neurodegeneration, has been implicated in Fe-S cluster assembly. We discovered a bypass mutation that enhances formation of the cluster scaffold intermediate. Further in depth study of how this frataxin bypass occurs should shed light on the process of mitochondrial Fe-S cluster assembly and its regulatory controls.
Rotation Projects (genetic and biochemical)
1. Genetic screen in yeast involving randomization of Isu1 scaffold and isolation of novel suppressor mutants altering Fe-S cluster assembly in mitochondria.
2. Genetic screen in yeast for escape from glutaredoxin deficiency in a grx3/4 minus background.
3. Phenotypic evaluation of a library of essential genes for novel iron trafficking genes/functions.
4. Purification of a 4 way complex (Nfs1/Isd11/Isu1/Yfh1) and characterization of its activity in Fe-S cluster formation on the scaffold.