Froschauer EM, Rietzschel N, Hassler MR, Binder M, Schweyen RJ, Lill R, Muehlenhoff U, Wiesenberger G

Mitochondrial iron uptake is of key importance for both organelle function and cellular iron homeostasis. The mitochondrial carrier family members Mrs3 and Mrs4 (homologs of vertebrate mitoferrin) function in organellar iron supply, yet other low efficiency transporters may exist. In S. cerevisiae, overexpression of RIM2 (MRS12) encoding a mitochondrial pyrimidine ...

Read More

nucleotide transporter can overcome the iron-related phenotypes of strains lacking both MRS3 and MRS4. Here, we show by in vitro transport studies that Rim2 mediates the transport of iron and other divalent metal ions across the mitochondrial inner membrane in a pyrimidine nucleotide-dependent fashion. Mutations in the proposed substrate binding site of Rim2 prevent both pyrimidine nucleotide and divalent ion transport. These results document that Rim2 catalyzes the co-import of pyrimidine nucleotides and divalent metal ions including ferrous iron. The deletion of RIM2 alone has no significant effect on mitochondrial iron supply, Fe/S protein maturation and heme synthesis. However, RIM2 deletion in mrs3/4D cells aggravates their Fe/S protein maturation defect. We conclude that under normal physiological conditions Rim2 does not play a significant role in mitochondrial iron acquisition, yet in the absence of the main iron transporters Mrs3-Mrs4 this carrier can supply the mitochondrial matrix with iron in a pyrimidine nucleotide-dependent fashion.

Date: Jun. 26, 2013

View in: Pubmed Google Scholar

156317