Iron‑sulfur clusters are essential cofactors found across all domains of life. Their assembly and transfer are accomplished by highly conserved protein complexes and partners. In eukaryotes a [2Fe-2S] cluster is first assembled in the mitochondria on the iron‑sulfur cluster scaffold protein ISCU in tandem with iron, sulfide, and electron donors. Current models suggest that a chaperone pair interacts with a cluster-bound ISCU to facilitate cluster transfer to a monothiol glutaredoxin. In humans this protein is glutaredoxin 5 (GLRX5) and the cluster can then be exchanged with a variety of target apo proteins. By use of circular dichroism spectroscopy, the kinetics of cluster exchange reactivity has been evaluated for human GLRX5 with a variety of cluster donor and acceptor partners, and the role of chaperones determined for several of these. In contrast to the prokaryotic model, where heat-shock type chaperone proteins HscA and HscB are required for successful and efficient transfer of a [2Fe-2S] cluster from the ISCU scaffold to a monothiol glutaredoxin. However, in the human system the chaperone homologs, HSPA9 and HSC20, are not necessary for human ISCU to promote cluster transfer to GLRX5, and appear to promote the reverse transfer. Cluster exchange with the human iron‑sulfur cluster carrier protein NFU1 and ferredoxins (FDX's), and the role of chaperones, has also been evaluated, demonstrating in certain cases control over the directionality of cluster transfer. In contrast to other prokaryotic and eukaryotic organisms, NFU1 is identified as a more likely physiological donor of [2Fe-2S] cluster to human GLRX5 than ISCU.

铁硫簇是生活各个领域中必不可少的辅助因子。它们的组装和转移是由高度保守的蛋白质复合物和伴侣完成的。在真核生物中，[2Fe-2S]簇首先在线粒体中组装在铁硫簇支架蛋白ISCU上，与铁，硫化物和电子供体串联。当前模型表明，伴侣对与簇结合的ISCU相互作用，以促进簇转移至单硫醇戊二醛毒素。在人类中，这种蛋白质是戊二醛毒素5（GLRX5），然后该簇可以与多种目标载脂蛋白交换。通过使用圆二色性光谱，已评估了具有多种簇供体和受体伴侣的人GLRX5的簇交换反应动力学，并确定了其中一些伴侣的作用。与原核模型相反，在原核模型中，热休克型分子伴侣蛋白HscA和HscB是成功地将[2Fe-2S]簇从ISCU支架成功转移至单硫醇戊二醛毒素所必需的。但是，在人类系统中，伴侣分子同源物HSPA9和HSC20对于人类ISCU促进簇转移至GLRX5并不是必需的，并且似乎促进了反向转移。还评估了与人类铁硫簇载体蛋白NFU1和铁氧还蛋白（FDX's）的簇交换，以及伴侣蛋白的作用，在某些情况下证明了对簇转移方向的控制。与其他原核和真核生物相反，NFU1被确定为比ISCU更可能是人GLRX5的[2Fe-2S]簇的生理供体。此处需要热休克型分子伴侣蛋白HscA和HscB才能成功有效地将[2Fe-2S]簇从ISCU支架转移至单硫醇戊二醛。但是，在人类系统中，伴侣分子同源物HSPA9和HSC20对于人类ISCU促进簇转移至GLRX5并不是必需的，并且似乎促进了反向转移。还评估了与人类铁硫簇载体蛋白NFU1和铁氧还蛋白（FDX's）的簇交换，以及伴侣蛋白的作用，在某些情况下证明了对簇转移方向的控制。与其他原核和真核生物相反，NFU1被确定为比ISCU更可能是人GLRX5的[2Fe-2S]簇的生理供体。此处需要热休克型分子伴侣蛋白HscA和HscB才能成功有效地将[2Fe-2S]簇从ISCU支架转移至单硫醇戊二醛。但是，在人类系统中，伴侣分子同源物HSPA9和HSC20对于人类ISCU促进簇转移至GLRX5并不是必需的，并且似乎促进了反向转移。还评估了与人类铁硫簇载体蛋白NFU1和铁氧还蛋白（FDX's）的簇交换，以及伴侣蛋白的作用，在某些情况下证明了对簇转移方向的控制。与其他原核和真核生物相反，NFU1被确定为比ISCU更可能是人GLRX5的[2Fe-2S]簇的生理供体。