10/31/2016 - RGD releases two interactive diagram pages for the mitochondrial iron-sulfur cluster protein biogenesis and the cytosolic iron-sulfur cluster protein assembly pathways

The small inorganic iron-sulfur (Fe-S) cluster (ISC) cofactor acts as an electron carrier in redox and catalytic reactions, and as a sulfur donor and environmental sensor. The ISC proteins in mitochondria, cytoplasm and nucleus are involved in many important cellular functions. The steps in the assembly of ISCs and delivery to Fe-S proteins are part of the mitochondrial ISC biogenesis and the connected cytosolic assembly (CIA) pathways; ISCs provide for the maturation of all Fe-S proteins. A subset of the mitochondrial ISC pathway, termed ‘core’, and the mitochondrial ISC transport are essential for the function of the CIA pathway.
Mitochondrial iron-sulfur cluster protein biogenesis pathway

Cytosolic iron-sulfur cluster protein assembly pathway

The mitochondrial pathway is essential for the maturation of all Fe-S proteins. It starts with the de novo assembly of a [2Fe-2S] cluster on a scaffold protein. Several more steps are part of a ‘core’ subset involved in further cluster assembly and delivery; the ‘core’ is essential for the function of the cytosolic pathway. Beyond, the ‘core’, there are the components involved in the assembly and delivery of mitochondrial [4Fe-4S] clusters. Click here to explore the details of this important system. A species still to be characterized, termed ‘X-S’ is delivered to the cytosol by the mitochondrial export pathway. An initial [4Fe-4S] cluster is assembled, followed by its maturation, transfer and final insertion into recipient proteins via a targeting complex. Particular combinations of targeting proteins deliver the cluster to specific cytosolic and nuclear recipient apoproteins. Click here to find out more about this pathway.