Mathematical Biology Seminar

Diane Ward
Department of Pathology, University of Utah

Genetic Analysis of Mitochondrial Iron Metabolism

Wednesday, November 19, 2014, at 3:05pm
LCB 219

Our goal is to define mitochondrial iron metabolism in eukaryotes at the molecular and biochemical level by studying proteins required for mitochondrial iron transport and utilization. We have identified mitochondrial iron importers in yeast, Mrs3/Mrs4, and vertebrates, Mitoferrin1 and Mitoferrin2. We demonstrated that the mitoferrins show tissue specific expression patterns and tissue specific functions. We have generated mice with floxed alleles of both Mitoferrin1 and Mitoferrin2. We are utilizing specific expression of Cre recombinase to identify the tissue specific function of the mitoferrins. We have determined that Mitoferrin1 is essential for vertebrate life and that the loss of Mitoferrin1 results in defects in red blood cell formation. We have further determined that when the liver is stressed to make more heme loss of Mitoferrin1 results in bridging fibrosis and cholestasis in the liver, a phenotype resembling erythropoietic protoporphyria. Our data suggest that Mitoferrin1 is important in B cells and we are testing its relevance in neuronal tissues, skeletal muscle and heart. Loss of Mitoferrin2 is not embryonic lethal, however, males show reduced numbers of sperm and decreased reproductive capability. Further, when Mitoferrin2 knockout mice are limited for iron in their diet, they develop a "fatty liver" disease. We are performing metabolic studies to understand the cause of the fatty liver phenotype.