|Rim2, pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria.|
Yoon H, Zhang Y, Pain J, Lyver ER, Lesuisse E, Pain D, Dancis A
Biochem J (2011)
Category: iron, iron-sulfur clusters, mitochondria-biogenesis, mitochondria-transport ¤ Added: Oct 27, 2011 ¤ Rating: ◊◊
Mitochondria transport and utilize iron for the synthesis of heme and Fe-S clusters. Although many proteins are known to be involved in these processes, additional proteins are likely to participate. To test this hypothesis, we used a genetic screen looking for yeast mutants that are synthetically lethal with the mitochondrial iron carriers, Mrs3 and Mrs4. Several genes were identified including an isolate mutated for Yfh1, the yeast frataxin homolog. All such triple mutants were complemented by increased expression of Rim2, another mitochondrial carrier protein. Rim2 overexpression was able to enhance heme and Fe-S cluster synthesis in wild-type or mrs3/mrs4 backgrounds. Conversely Rim2 depletion impaired heme and Fe-S cluster synthesis in wild-type or mrs3/mrs4 backgrounds, indicating a unique requirement of this mitochondrial transporter for these processes. Rim2 was previously shown to mediate pyrimidine exchange in and out of vesicles. Here we found that isolated mitochondria lacking Rim2 exhibited concordant iron defects and pyrimidine transport defects, although the connection between these two functions is not explained. When organellar membranes were ruptured to bypass iron transport, heme synthesis from added iron and porphyrin was still markedly deficient in Rim2 depleted mitochondrial lysate. The data indicate that Rim2 is a pyrimidine exchanger with an additional unique function in promoting mitochondrial iron utilization.