| dc.description.abstract | The mitochondrion is a double membrane-bound organelle found in all eukaryotic organisms.
Mitochondria are endosymbiotic, autogenous organelles referred to as “Powerhouse” of cells due
to their ability to synthesize ATP from oxidative phosphorylation. The number of mitochondria
varies from cell to cell in an organism, depending on the function of the cells. For example, liver
and muscle cells are rich in mitochondria, on the other hand, RBC cells are devoid of
mitochondria. In healthy cells, mitochondrial homeostasis is mainly due to Biogenesis (fission
and fusion), maintenance (recycling) and clearance. Mitochondria also act as a molecular sink to
regulate the activities of many proteins. In Eukaryotes mitochondria are the major hub for the
synthesis of Fe-S clusters.
The Fe-S cluster biogenesis process is essentially constituted of two major events; first,
the assembly of Fe-S clusters on a scaffold protein. Second, the transfer of the assembled Fe-S
clusters to a recipient apo-protein. In Eukaryotic mitochondria, the sulfur transfer was
accomplished by cysteine desulfurase protein NFS1, which was stabilized by ISD11 protein.
ISD11 protein exclusively presents only in the eukaryotic system and absent in bacteria. On the
other hand, the iron-binding protein frataxin donates Iron. The electrons required for the process
of Fe-S cluster biogenesis was provided by ferredoxin reductase and ferredoxin 2. A highly
conserved matrix protein ISCU acts as the scaffold where the assembly of Fe-S cluster occurs.
The transfer of Fe-S cluster process is mediated by chaperone machinery comprising the
mtHsp70 namely HSPA9, the J-protein cochaperone, HSCB along GLRX5. However, transfer of
Fe-S clusters to apoprotein was not clearly understood.
Dysfunction of Mitochondrial proteins involved in Fe-S cluster biogenesis and
transfer leads to a pathological condition in humans. For example, deficiency or loss of function
of scaffold protein ISCU, iron donor protein frataxin, sulfur donor protein NFS1, sulfur transfer
assisting protein, ISD11 and electron transfer protein FDX2 results in mitochondrial disorders
ISCU myopathy, Friedreich’s ataxia, Infantile Mitochondrial Complex II/III Deficiency
(IMC23D), Combined Oxidative Phosphorylation Deficiency19 (COXPD19) and FDX2
myopathy respectively. | en_US |
