J-domain Protein, Jac1p, of Yeast Mitochondria Required for Iron Homeostasis and Activity of Fe-S Cluster Proteins

• Published in: The Journal of biological chemistry Vol. 276; no. 20; pp. 17524 - 17532
• Main Authors: Kim, Roy, Saxena, Sandeep, Gordon, Donna M., Pain, Debkumar, Dancis, Andrew
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.05.2001; American Society for Biochemistry and Molecular Biology
• Subjects: Aconitate Hydratase - metabolism; Fungal Proteins - metabolism; Hemeproteins - metabolism; Homeostasis; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Iron - metabolism; iron-sulfur protein; Iron-Sulfur Proteins - metabolism; jac1 gene; Jac1 protein; Mitochondria - metabolism; Mitochondrial Proteins; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Mutagenesis; Phenotype; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; ssq1 gene; Ssq1 protein; Succinate Dehydrogenase - metabolism; Ultraviolet Rays
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M010695200

J-proteins are molecular chaperones with a characteristic domain predicted to mediate interaction with Hsp70 proteins. We have previously isolated yeast mutants of the mitochondrial Hsp70, Ssq1p, in a genetic screen for mutants with altered iron homeostasis. Here we describe the isolation of mutants of the J-domain protein, Jac1p, using the same screen. Mutantjac1 alleles predicted to encode severely truncated proteins (lacking 70 or 152 amino acids) were associated with phenotypes strikingly similar to the phenotypes of ssq1mutants. These phenotypes include activation of the high affinity cellular iron uptake system and iron accumulation in mitochondria. In contrast to iron accumulation, Fe-S proteins of mitochondria were specifically deficient. In jac1 mutants, like inssq1 mutants, processing of the Yfh1p precursor protein from intermediate to mature forms was delayed. In the genetic backgrounds used in this study, jac1 null mutants were found to be viable, permitting analysis of genetic interactions. TheΔjac1 Δssq1 double mutant was more severely compromised for growth than either single mutant, suggesting a synthetic or additive effect of these mutations. Overexpression of Jac1p partially suppressed ssq1 slow growth and vice versa. Similar mitochondrial localization and similar mutant phenotypes suggest that Ssq1p and Jac1p are functional partners in iron homeostasis.