Mechanisms of iron-sulfur protein maturation in mitochondria, cytosol and nucleus of eukaryotes.
Iron-sulfur (Fe/S) clusters are important cofactors of numerous proteins involved in electron transfer, metabolic and regulatory processes. In eukaryotic cells, known Fe/S proteins are located within mitochondria, the nucleus and the cytosol. Over the past years the molecular basis of Fe/S cluster synthesis and incorporation into apoproteins in a living cell has started to become elucidated. Biogenesis of these simple inorganic cofactors is surprisingly complex and, in eukaryotes such as Saccharomyces cerevisiae, is accomplished by three distinct proteinaceous machineries. The "iron-sulfur cluster (ISC) assembly machinery" of mitochondria was inherited from the bacterial ancestor of mitochondria. ISC components are conserved in eukaryotes from yeast to man. The key principle of biosynthesis is the assembly of the Fe/S cluster on a scaffold protein before it is transferred to target apoproteins. Cytosolic and nuclear Fe/S protein maturation also requires the function of the mitochondrial ISC assembly system. It is believed that mitochondria contribute a still unknown compound to biogenesis outside the organelle. This compound is exported by the mitochondrial "ISC export machinery" and utilised by the "cytosolic iron-sulfur protein assembly (CIA) machinery". Components of these two latter systems are also highly conserved in eukaryotes. Defects in the mitochondrial ISC assembly and export systems, but not in the CIA machinery have a strong impact on cellular iron uptake and intracellular iron distribution showing that mitochondria are crucial for both cellular Fe/S protein assembly and iron homeostasis.
Lill
Roland
R
Institut für Zytobiologie, Philipps Universität Marburg, Robert-Koch-Strasse 6, 35037 Marburg, Germany. lill@staff.uni-marburg.de
Dutkiewicz
Rafal
R
Elsässer
Hans-Peter
HP
Hausmann
Anja
A
Netz
Daili J A
DJ
Pierik
Antonio J
AJ
Stehling
Oliver
O
Urzica
Eugen
E
Mühlenhoff
Ulrich
U
D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D007506:Iron-Sulfur Proteins