Figure 3.

Export of mitochondrial iron and iron-containing cofactors: Iron is exported from mitochondria as heme or metal ions in low-molecular-mass complexes. Additionally, a presently unidentified intermediate required for cytosolic ISC biogenesis is also exported from mitochondria. In yeast, three inner mitochondrial membrane iron exporters have been identified: Mmt1, Mmt2, and Mtm1. In the case of heme export, FLVCR1b is postulated to play a role, but it is unclear where FLVCR1b localizes within the mitochondrion or to what extent it facilitates heme export. The ISC intermediate necessary for cytosolic ISC biogenesis is trafficked across the inner mitochondrial membrane by Atm1 in yeast and ABCB7 in mammals. Methods of export across the outer mitochondrial membrane remain unknown. It is hypothesized that various protein channels allow for the flow of these iron species, and that iron and cofactor chaperones directly accept or extract their cargo from the mitochondrion. A non-protein-based mechanism for iron, heme, and ISC intermediate export is also possible via mitochondria-derived vesicles (MDVs) and compartments (MDCs).