AN ENZYME IN YEAST MITOCHONDRIA THAT CATALYZES A STEP IN BRANCHED-CHAIN AMINO-ACID BIOSYNTHESIS ALSO FUNCTIONS IN MITOCHONDRIAL-DNA STABILITY

The yeast mitochondrial high mobility group protein Abf2p is required, under certain growth conditions, for the maintenance of wild-type (rh o(+)) mitochondrial DNA (mtDNA). We have identified a multicopy suppre ssor of the mtDNA instability phenotype of cells with a null allele of the ABF2 gene (Delta abf2). The suppressor is a known gene, ILV5, enc oding the mitochondrial protein, acetohydroxy acid reductoisomerase, w hich catalyzes a step in branched-chain amino acid biosynthesis. Effic ient 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, cha nges 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 il nu 5), leading to the pr oduction of mostly rho(-) petite mutants. The instability of rho(+) mt DNA in Delta il nu 5 cells is not simply a consequence of a block in b ranched-chain amino acid biosynthesis, since mtDNA is stable in cells with a null allele of the ILV2 gene, which encodes another enzyme of t hat pathway. The most severe instability of rho(+) mtDNA is observed i n 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.