The Nfs1 interacting protein Isd11 has an essential role in Fe/S cluster biogenesis in mitochondria.
Formation of iron/sulfur (Fe/S) clusters, protein translocation and protein folding are essential processes in the mitochondria of Saccharomyces cerevisiae. In a systematic approach to characterize essential proteins involved in these processes, we identified a novel essential protein of the mitochondrial matrix, which is highly conserved from yeast to human and which we termed Isd11. Depletion of Isd11 caused a strong reduction in the levels of the Fe/S proteins aconitase and the Rieske protein, and a massive decrease in the enzymatic activities of aconitase and succinate dehydrogenase. Incorporation of iron into the Fe/S protein Leu1 and formation of the Fe/S cluster containing holoform of the mitochondrial ferredoxin Yah1 were inhibited in the absence of Isd11. This strongly suggests that Isd11 is required for the assembly of Fe/S proteins. We show that Isd11 forms a stable complex with Nfs1, the cysteine desulfurase of the mitochondrial machinery for Fe/S cluster assembly. In the absence of Isd11, Nfs1 is prone to aggregation. We propose that Isd11 acts together with Nfs1 in an early step in the biogenesis of Fe/S proteins.
Adam
Alexander C
AC
Institut für Physiologische Chemie, Universität München, München, Germany.
Bornhövd
Carsten
C
Prokisch
Holger
H
Neupert
Walter
W
Hell
Kai
K
D000595:Amino Acid Sequence; D013437:Carbon-Sulfur Lyases / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D015536:Down-Regulation; D007506:Iron-Sulfur Proteins / Q000096:biosynthesis* / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013466:Sulfurtransferases
D007506:Iron-Sulfur Proteins; C508374:Isd11 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D013466:Sulfurtransferases; C115912:NFS1 protein, S cerevisiae; D013437:Carbon-Sulfur Lyases; C080546:cysteine desulfurase; D003545:Cysteine