Mitochondrial Isa2p plays a crucial role in the maturation of cellular iron-sulfur proteins

The assembly of iron-sulfur (Fe/S) clusters in a living cell is mediated by a complex machinery which, in eukaryotes, is localised within mitochondria . Here, we report on a new component of this machinery, the protein Isa2p o f the yeast Saccharomyces cerevisiae. The protein shares sequence similarit y with yeast Isa1p and the bacterial IscA proteins which recently have been shown to perform a function in Fe/S cluster biosynthesis. Like the Isa1p h omologue, Isa2p is localised in the mitochondrial matrix as a soluble prote in. Deletion of the ISA2 gene results in the loss of mitochondrial DNA and a strong growth defect. Simultaneous deletion of the ISA1 gene does not fur ther exacerbate this growth phenotype suggesting that the Isa proteins perf orm a non-essential function. When Isa2p was depicted by regulated gene exp ression, mtDNA was maintained, but cells grew slowly on non-fermentable car bon sources. The maturation of both mitochondrial and cytosolic Fe/S protei ns was strongly impaired in the absence of Isa2p. Thus, Isa2p is a new memb er of the Fe/S cluster biosynthesis machinery of the mitochondrial matrix a nd may be involved in the binding of an intermediate of Fe/S cluster assemb ly. (C) 2000 Federation of European Biochemical Societies. Published by Els evier Science B.V. All rights reserved.