Year: 2017
Type: dissertation
Abstract: Fe-S clusters are ubiquitous protein cofactors highly conserved from bacteria to human. Practically, they play a crucial and essential role in every living cell. Fe-S cluster are indispensable for life because of the ability of the iron to accept or donate electrons, formally altering between the ferrous (Fe2+) and ferric (Fe3+) oxidation states. \nThe synthesis of Fe-S clusters and their insertion into apo proteins requires almost 30 proteins in the mitochondria and cytosol of eukaryotic cells. Three distinct protein machineries are required in the (non-plant) eukaryotic cells for the biogenesis of the Fe-S clusters: \n ISC assembly machinery in mitochondria (inherited from bacteria during evolution) \n ISC export machinery located in the mitochondrial inter membrane space, \ncytosolic ISC assembly machinery (CIA) \nMaturation of its Fe-S clusters strictly depends on the two mitochondrial ISC systems and the CIA machinery providing a tight link between mitochondrial function and cytosolic protein translation. Most of the ISC and CIA components are essential for the viability of the human cells. Fe-S clusters are essential cofactors of many proteins so the disruption of their biosynthesis leads to dysfunction of many fundamental cellular processes. The central importance of Fe-S-protein biogenesis in mammal’s is impressively documented in numerous diseases associated with defects in Fe-S-protein biogenesis components or Fe-S proteins. \nIn my research, I used a multidisciplinary approach to integrate different scientific fields for the common aim to solve the maturation pathway of some Fe-S proteins.
Author: Riccardo Muzzioli
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: green
Award: G7062140657
OpenAlex ID: W2713822076