A member of the YER057c/yjgf/Uk114 family links isoleucine biosynthesis and intact mitochondria maintenance in Saccharomyces cerevisiae

Background: Two paralogs, YIL051c and YER057c, in the Saccharomyces cerevis iae genome are members of the YER057c/Yigf/Uk114 family, which is highly co nserved among Eubacteria, Archaea and Eukarya. Although the molecular funct ion of this protein family is not clear, previous studies suggest that it p lays a role in the regulation of metabolic pathways and cell differentiatio n. Results: Yil051cp is 70% identical in amino acid sequence to Yer057cp, and differs in that the former is longer by 16 amino acids containing, in part, the mitochondrial targeting signal at the N-terminus of the protein. An HA -tagged protein of Yil051cp is localized strictly in mitochondria, while th at of Yer057cp is found in both cytoplasm and nucleus. Disruption of YIL051 c (yil051c Delta) resulted in severe growth retardation in glucose medium d ue to isoleucine auxotroph, and no growth in glycerol medium due to the los s of mitochondria. An extract prepared from yil051c Delta cells showed no t ransaminase activity for isoleucine, while that for valine or leucine was i ntact. Haploid yil051c Delta cells newly isolated from the YIL051c/yil051c Delta hetero-diploids gradually lost mitochondrial DNA within 24 h in the a bsence of, but not in the presence of, an isoleucine. Mutants either requir ing leucine (leu2-112) or isoleucine-valine (bat1 Delta, bat2 Delta) in a Y IL051c background showed no changes in mitochondrial DNA maintenance in the absence of requirements. Conclusions: Based on these results, we named Yil051c as Ibm1 (Isoleucine B iosynthesis and Mitochondria maintenance1) and concluded that: (i) Ibm1p de termines the specificity of isoleucine biosynthesis, probably at the transa mination step, (ii) Ibm1p is required for the maintenance of mitochondrial DNA when isoleucine is deficient, and (iii) Isoleucine compensates for the lack of Ibm1p. Taken together, Ibm1p may act as a sensor for isoleucine def iciency as well as a regulator determining the specificity for branched ami no acid transaminase.