J-domain protein, Jac1p, of yeast mitochondria required for iron homeostasis and activity of Fe-S cluster proteins

J-proteins are molecular chaperones with a characteristic domain predicted to mediate interaction with Hsp70 proteins. We have previously isolated yea st mutants of the mitochondrial Hsp70, Ssq1p, in a genetic screen for mutan ts with altered iron homeostasis. Here we describe the isolation of mutants of the J-domain protein, Jac1p, using the same screen. Mutant jac1 alleles predicted to encode severely truncated proteins (lacking 70 or 152 amino a cids) were associated with phenotypes strikingly similar to the phenotypes of ssq1 mutants. These phenotypes include activation of the high affinity c ellular iron uptake system and iron accumulation in mitochondria. In contra st to iron accumulation, Fe-S proteins of mitochondria were specifically de ficient, In jac1 mutants, like in ssq1 mutants, processing of the Yfh1p pre cursor protein from intermediate to mature forms was delayed. In the geneti c backgrounds used in this study, jac1 null mutants were found to be viable , permitting analysis of genetic interactions. The Delta jac1 Delta ssq1 do uble mutant was more severely compromised for growth than either single mut ant, suggesting a synthetic or additive effect of these mutations. Overexpr ession of Jac1p partially suppressed ssq1 slow growth and vice verse. Simil ar mitochondrial localization and similar mutant phenotypes suggest that Ss q1p and Jac1p are functional partners in iron homeostasis.