Mitochondrial-type iron–sulfur cluster biosynthesis genes (IscS and IscU) in the apicomplexan Cryptosporidium parvum

Abstract

Several reports have indicated that the iron-sulfur cluster [Fe-S] assembly machinery in most eukaryotes is confined to the mitochondria and chloroplasts. The best-characterized and most highly conserved [Fe-S] assembly proteins are a pyridoxal-59-phosphate-dependent cysteine desulfurase (IscS), and IscU, a protein functioning as a scaffold for the assembly of [Fe-S] prior to their incorporation into apoproteins. In this work, genes encoding IscS and IscU homologues have been isolated and characterized from the apicomplexan parasite Cryptosporidium parvum, an opportunistic pathogen in AIDS patients, for which no effective treatment is available. Primary sequence analysis (CpIscS and CpIscU) and phylogenetic studies (CpIscS) indicate that both genes are most closely related to mitochondrial homologues from other organisms. Moreover, the N-terminal signal sequences of CpIscS and CpIscU predicted in silico specifically target green fluorescent protein to the mitochondrial network of the yeast Saccharomyces cerevisiae. Overall, these findings suggest that the previously identified mitochondrial relict of C. parvum may have been retained by the parasite as an intracellular site for [Fe-S] assembly.

Multiple secondary origins of the anaerobic lifestyle in eukaryotes

“…Posterior probabilities for some groups are shown, with a value of 1.0 representing maximum support. The strongly supported groups have also been recovered in previously published analyses using different methods, including maximum-likelihood, and different support measures including bootstrapping (Horner et al 1999;Rotte et al 2001). examined (Katinka et al 2001;LaGier et al 2003; but only the Trichomonas hydrogenosome (Sutak et al 2004) and Giardia mitosome (Tovar et al 2003) have actually been demonstrated to contain the pathway. Entamoeba is so far unique among eukaryotes in that it has lost the mitochondrial homologues of IscS and IscU (Loftus et al 2005), and instead it possesses genes for the homologous proteins NifS and NifU, acquired through horizontal gene transfer from a bacterium related to Campylobacter (Ali et al 2004;van der Giezen et al 2004).…”

Frataxin, a Conserved Mitochondrial Protein, in the Hydrogenosome of Trichomonas vaginalis

“…Defects in the expression of components involved in FeS cluster synthesis often have dramatic or even lethal consequences for the whole organism. Consequently, it has been suggested that FeS cluster synthesis might be the critical indispensable function of mitochondria and of the mitochondrial homologues, hydrogenosomes and mitosomes, recently identified in some microaerophilic and parasitic unicellular eukaryotes (22,38,41). The finding of a frataxin homologue in the hydrogenosomes of T. vaginalis prompted us to search for frataxin homologues in the genomes of these unicellular eukaryotes.…”

Lipoic Acid Metabolism in Microbial Pathogens

“…The parasite does contain a highly reduced two-membrane compartment called the mitosome that is thought to have descended from a common ancestral apicomplexan mitochondrion (82,180). This organelle appears to have been retained to carry out a limited number of metabolic functions, such as the synthesis of iron-sulfur clusters (116). The KDH complex found in the P. falciparum and T. gondii mitochondria is absent from C. parvum, as this parasite relies solely on anaerobic metabolism.…”