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SUMMARY:Feldberg Prize Lecture: Biogenesis of iron-sulfur proteins in euka
 ryotes - Professor Roland Lill\, Philipps University Marburg\, Germany
DTSTART:20110415T151500Z
DTEND:20110415T170000Z
UID:TALK30059@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Iron-sulfur (Fe/S) clusters are simple and evolutionary ancien
 t inorganic cofactors of proteins with a function in catalysis\, electron 
 transfer and regulation. The molecular basis of Fe/S cluster synthesis and
  its assembly into apoproteins in a living cell has been subject to intens
 e research activities over the past years (see Reviews). Biogenesis is acc
 omplished by three complex proteinaceous machineries (Figure). Mitochondri
 al Fe/S proteins require the iron-sulfur cluster (ISC) assembly machinery 
 which was inherited from bacteria during evolution. Cytosolic and nuclear 
 Fe/S protein assembly also depends on the function of this machinery\, yet
  additionally requires the mitochondrial ISC export apparatus and the cyto
 solic iron-sulfur protein assembly (CIA) machinery. General principles see
 m to underlie the assembly processes in both the mitochondria and the cyto
 sol/nucleus\, even though the ISC and CIA components do not show any simil
 arity (Lill\, 2009). The components of all three systems (more than 25 pro
 teins) are highly conserved from yeast to man suggesting similar mechanism
 s of Fe/S protein assembly in all eukaryotes. Defects in Fe/S protein biog
 enesis result in the loss of cell viability. This is due to essential cyto
 solic and nuclear Fe/S proteins involved in DNA replication and repair as 
 well as ribosome assembly and function. The dependence of their assembly o
 n mitochondria explains why mitochondria (or mitochondria-derived organell
 es such as mitosomes and hydrogenosomes) are indispensable in virtually al
 l eukaryotic cells\, and show the crucial function of mitochondria in basi
 c processes of DNA and RNA metabolism. \nFe/S protein biogenesis is of imp
 ortance for human disease in that more than ten diseases are associated wi
 th ISC\, CIA or Fe/S protein defects. For instance\, depletion of the ISC 
 assembly component frataxin leads to the neurodegenerative disease Friedre
 ich’s ataxia\, and a defect in the ISC export protein ABCB7 is associate
 d with X-linked sideroblastic anemia and ataxia (XLSA/A). Fe/S protein def
 ects in nuclear DNA replication and repair proteins link Fe/S protein biog
 enesis to numerous diseases including various forms of cancer. \n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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