title: An enzyme in yeast mitochondria that catalyzes a step in branched-chain amino acid biosynthesis also functions in mitochondrial DNA stability.
abstract: The yeast mitochondrial high mobility group protein Abf2p is required, under certain growth conditions, for the maintenance of wild-type (rho+) mitochondrial DNA (mtDNA). We have identified a multicopy suppressor of the mtDNA instability phenotype of cells with a null allele of the ABF2 gene (delta abf2). The suppressor is a known gene, ILV5, encoding the mitochondrial protein, acetohydroxy acid reductoisomerase, which catalyzes a step in branched-chain amino acid biosynthesis. Efficient suppression occurs with just a 2- to 3-fold increase in ILV5 copy number. Moreover, in delta abf2 cells with a single copy of ILV5, changes in mtDNA stability correlate directly with changes in conditions that are known to affect ILV5 expression. Wild-type mtDNA is unstable in cells with an ILV5 null mutation (delta ilv5), leading to the production of mostly rho- petite mutants. The instability of rho+ mtDNA in delta ilv5 cells is not simply a consequence of a block in branched-chain amino acid biosynthesis, since mtDNA is stable in cells with a null allele of the ILV2 gene, which encodes another enzyme of that pathway. The most severe instability of rho+ mtDNA is observed in cells with null alleles of both ABF2 and ILV5. We suggest that ILV5 encodes a bifunctional protein required for branched-chain amino acid biosynthesis and for the maintenance of rho+ mtDNA.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: O
authors.initials: O
authors.lastname: Zelenaya-Troitskaya
authors.forename: P S
authors.initials: PS
authors.lastname: Perlman
authors.forename: R A
authors.initials: RA
authors.lastname: Butow
mesh_terms: D015072:2-Acetolactate Mutase / Q000096:biosynthesis / Q000235:genetics; D000483:Alleles; D000597:Amino Acids, Branched-Chain / Q000096:biosynthesis*; D001483:Base Sequence; D002874:Chromosome Mapping; D004271:DNA, Fungal / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005809:Genes, Regulator; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C072843:ABF2 protein, S cerevisiae; D000597:Amino Acids, Branched-Chain; D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D015072:2-Acetolactate Mutase