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 have been 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. In particular, demand created by continuous protein turnover and the sacrificial destruction of clusters for synthesis of biotin and lipoic acid reveal possible bottlenecks in the supply chain of Fe-S clusters. Taking available information from other species into consideration, this review explores the mitochondrial assembly machinery of Arabidopsis and provides 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 a sulfur source. After extraction of sulfur atoms from these clusters, the remains of the clusters probably fall apart, releasing sulfide as a highly toxic by-product. Immediate refixation through local cysteine biosynthesis is therefore an essential salvage pathway and emphasizes the physiological need for cysteine biosynthesis in plant mitochondria. Analysis of molecular mechanisms for assembly, transfer, and turnover of mitochondrial iron-sulfur clusters reveals bottlenecks in cluster supply and proteins with particularly high demand for cluster replenishment.

Automated summary

Significant efforts have been made to examine the nature of the autonomous iron-sulfur (Fe-S) cluster assembly machinery in mitochondria. The synthesis and assembly of Fe-S clusters occur in two distinct steps, but the transfer and distribution among their respective apoproteins are still not well understood. This review explores the mitochondrial assembly machinery of Arabidopsis and highlights the demand for cluster replenishment and the essential salvage pathway in plant mitochondria.