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 cerevisiae genome are members of the YER057c/Yigf/Uk114 family, which is highly conserved among Eubacteria, Archaea and Eukarya. Although the molecular function of this protein family is not clear, previous studies suggest that it plays a role in the regulation of metabolic pathways and cell differentiation.


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 that of Yer057cp is found in both cytoplasm and nucleus. Disruption of YIL051c (yil051cDelta) resulted in severe growth retardation in glucose medium due to isoleucine auxotroph, and no growth in glycerol medium due to the loss of mitochondria. An extract prepared from yil051cDelta cells showed no transaminase activity for isoleucine, while that for valine or leucine was intact. Haploid yil051cDelta cells newly isolated from the YIL051c/yil051cDelta hetero-diploids gradually lost mitochondrial DNA within 24 h in the absence of, but not in the presence of, an isoleucine. Mutants either requiring leucine (leu2-112) or isoleucine-valine (bat1Delta, bat2Delta) in a YIL051c background showed no changes in mitochondrial DNA maintenance in the absence of requirements.


CONCLUSIONS
Based on these results, we named Yil051c as Ibm1 (Isoleucine Biosynthesis and Mitochondria maintenance1) and concluded that: (i) Ibm1p determines the specificity of isoleucine biosynthesis, probably at the transamination 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 deficiency as well as a regulator determining the specificity for branched amino acid transaminase.
Kim
J M
JM
Department of Molecular Biology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma City, Nara 630-0101, Japan.
Yoshikawa
H
H
Shirahige
K
K
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D016681:Genome, Fungal; D007532:Isoleucine / Q000096:biosynthesis / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D016415:Sequence Alignment
D001426:Bacterial Proteins; C116617:YjgF protein, Bacteria; D007532:Isoleucine