FIGURE 8.

Working model for the assembly of mitochondrial [4Fe-4S] proteins. The maturation of all mitochondrial Fe/S proteins requires the de novo synthesis of a [2Fe-2S] cluster on the central scaffold proteins Isu1-Isu2 (cf. Ref. 10). This co-factor is released from Isu1-Isu2 with the help of the Hsp70 chaperone Ssq1 and its co-chaperone Jac1 and is inserted into [2Fe-2S] proteins. The maturation of [4Fe-4S] proteins additionally involves the specialized complex of Isa1, Isa2, and the tetrahydrofolate (THF)-binding protein Iba57. The Isa proteins bind iron that may be used for the formation of mitochondrial [4Fe-4S] proteins in a step involving Iba57. The biochemical mechanism of the generation of the [4Fe-4S] cluster, including the precise fate of Isa-bound iron, is unknown. (See “Discussion” for further details).