Molecular Details Of The Mitochondrial Iron Sulfur Cluster Assembly Pathway

<p>MOLECULAR DETAILS OF THE MITOCHONDRIAL IRON SULFUR CLUSTER ASSEMBLY PATHWAY</p> <p>Iron-sulfur clusters are an important class of prosthetic group involved in electron transfer, enzyme catalysis, and regulation of gene expression. Their biosynthesis requires complex machinery located within the mitochondrion since free iron and sulfide are extremely toxic to the cell. Defects in this pathway results in several diseases such as Friedreich's Ataxia (FRDA), Sideroblastic Anemia and ISCU Myopathy. Therefore molecular details of the biogenesis pathway will provide deep insight in the pathway and treatment options for these diseases. FRDA is caused by deficiency of a single protein called as `Frataxin'. Frataxin is a mitochondrial protein shown to regulate cellular iron homeostasis. Frataxin is highly conserved from prokaryotes to eukaryotes but its cellular function has not been completely characterized.</p> <p>The focus of the research presented in this dissertation is to characterize frataxin's interaction with the partner proteins during the iron sulfur cluster assembly pathway. This will provide us important information regarding modulation of metal delivery by frataxin and how it interacts with partner proteins, which can be used for treatment of several iron disregulation disorders. Research on two orthologs of frataxin (yeast and drosophila) is presented in this dissertation. Drosophila frataxin binds ferrous iron and exists as an alpha-beta sandwich structure. In both, yeast and drosophila, frataxin is able to deliver iron to Isu scaffold (on which transient cluster synthesis takes place) through a metal dependent protein protein interaction. Cluster binding stabilizes the fold of Isu scaffold protein. There is a separate initial metal loading site on ISU scaffold proteins other than the cysteine rich active site.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Biochemistry and Molecular Biology

Year dc:date.available

2011

Author dc:creator

• Rawat, Swati

Contributors dc:contributor

• Timothy Stemmler

• cysteine desulfurase
• Frataxin
• Iron
• Iron sulfur cluster biogenesis
• scaffold
• Biochemistry
• Molecular Biology

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/204

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-1203