Cytosolic iron–sulfur cluster transfer—a proposed kinetic pathway for reconstitution of glutaredoxin 3

Abstract

Iron–sulfur (Fe–S) clusters are ubiquitously conserved and play essential cellular roles. The mechanism of Fe–S cluster biogenesis involves multiple proteins in a complex pathway. Cluster biosynthesis primarily occurs in the mitochondria, but key Fe–S proteins also exist in the cytosol. One such protein, glutaredoxin 3 (Grx3), is involved in iron regulation, sensing, and mediating [2Fe-2S] cluster delivery to cytosolic protein targets, but the cluster donor for cytosolic Grx3 has not been elucidated. Herein, we delineate the kinetic transfer of [2Fe-2S] clusters into Grx3 from potential cytosolic carrier/scaffold proteins, IscU and Nfu, to evaluate a possible model for Grx3 reconstitution in vivo.