Assembly, transfer and fate of mitochondrial iron-sulfur clusters.

Since the discovery of an autonomous iron-sulfur cluster (Fe-S) assembly machinery in mitochondria, significant efforts to examine the nature of this process were made. The assembly of Fe-S clusters occurs in two distinct steps with the initial synthesis of [2Fe-2S] clusters by a first machinery followed by a subsequent assembly into [4Fe-4S] clusters by a second machinery. Despite this knowledge, we still have only a rudimentary understanding of how Fe-S clusters are transferred and distributed among their respective apoproteins. Especially considering that continuous protein turnover and particularly sacrificial destruction of clusters for synthesis of biotin and lipoic acid reveals possible bottlenecks in the supply chain of Fe-S clusters. Considering available information from other species, this review explores the mitochondrial assembly machinery of Arabidopsis and provides the current knowledge about the respective transfer steps to apoproteins. Furthermore, this review highlights biotin synthase and lipoyl synthase, which both utilize Fe-S clusters as sulfur source. After extraction of sulfur atoms from these clusters, the remains of the clusters likely fall apart releasing sulfide as a highly toxic by-product. Immediate refixation through local cysteine biosynthesis is therefore an essential salvage pathway and emphasises the physiological need for cysteine biosynthesis in plant mitochondria.