ISCU

Iron-sulfur (Fe-S) clusters are necessary for several mitochondrial enzymes and other subcellular compartment proteins. They contain sulfur and iron, and are created via several steps that include cysteine desulfurases, iron donors, chaperones, and scaffold proteins. This gene encodes the two isomeric forms, ISCU1 and ISCU2, of the Fe-S cluster scaffold protein. Mutations in this gene have been found in patients with myopathy with severe exercise intolerance and myoglobinuria. [provided by RefSeq]

Full Name

iron-sulfur cluster scaffold homolog (E. coli)

Function

Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins (PubMed:11060020).
First, a [2Fe-2S] cluster is transiently assembled on the scaffold protein ISCU. In a second step, the cluster is released from ISCU, transferred to a glutaredoxin GLRX5, followed by the formation of mitochondrial [2Fe-2S] proteins, the synthesis of [4Fe-4S] clusters and their target-specific insertion into the recipient apoproteins. Cluster assembly on ISCU depends on the function of the cysteine desulfurase complex NFS1-LYRM4/ISD11, which serves as the sulfur donor for cluster synthesis, the iron-binding protein frataxin as the putative iron donor, and the electron transfer chain comprised of ferredoxin reductase and ferredoxin, which receive their electrons from NADH (By similarity).
Isoform 2
Functions as a cytoplasmic scaffold protein for the de novo synthesis of iron-sulfur clusters in the cytoplasm.

Biological Process

Cellular iron ion homeostasisManual Assertion Based On ExperimentIBA:GO_Central
Iron-sulfur cluster assemblyManual Assertion Based On ExperimentTAS:UniProtKB
Negative regulation of iron ion import across plasma membraneManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of aconitate hydratase activityManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of mitochondrial electron transport, NADH to ubiquinoneManual Assertion Based On ExperimentIMP:ARUK-UCL

Cellular Location

Isoform 1: Mitochondrion
Isoform 2: Cytoplasm; Nucleus

Involvement in disease

Myopathy with exercise intolerance Swedish type (MEIS):
Autosomal recessive metabolic disease characterized by lifelong severe exercise intolerance, in which minor exertion causes fatigue of active muscles, shortness of breath, and cardiac palpitations in association with lactic acidosis. The biochemical phenotype is characterized by a deficiency in mitochondrial iron-sulfur proteins and impaired muscle oxidative metabolism.