The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation

• DOI: 10.1091/mbc.e11-09-0772
• Publication Date: 2012-02-10T05:25:35Z
• Authors: Alex D. Sheftel; Claudia Wilbrecht; Oliver Stehling; Brigitte Niggemeyer; Hans-Peter Elsässer; Ulrich Mühlenhoff; Roland Lill
• Keywords: DNAJA3

Members of the bacterial and mitochondrial iron-sulfur cluster (ISC) assembly machinery include so-called A-type ISC proteins, which support a subset Fe/S apoproteins. The human genome encodes two termed ISCA1 ISCA2, are related to Saccharomyces cerevisiae Isa1 Isa2, respectively. An additional protein, Iba57, physically interacts with Isa2 in yeast. To test cellular role ISCA1, IBA57, HeLa cells were depleted for any these proteins by RNA interference technology. Depleted contained massively swollen enlarged mitochondria that virtually devoid cristae membranes, demonstrating importance biogenesis. activities [4Fe-4S] including aconitase, respiratory complex I, lipoic acid synthase, diminished following depletion three proteins. In contrast, [2Fe-2S] enzyme ferrochelatase heme content unaffected. We further provide evidence against localization direct protein maturation function ISCA2 cytosol. Taken together, our data suggest IBA57 specifically involved functioning late pathway.