MITOCHONDRIAL AND CYTOSOLIC BRANCHED-CHAIN AMINO-ACID TRANSAMINASES FROM YEAST, HOMOLOGS OF THE MYC ONCOGENE-REGULATED ECA39 PROTEIN

We have isolated a high copy suppressor of a temperature-sensitive mut ation in ATM1, which codes for an ABC transporter of Saccharomyces cer evisiae mitochondria. The suppressor, termed BAT1, encodes a protein o f 393 amino acid residues with an NH2-terminal extension that directs Bat1p to the mitochondrial matrix, A highly homologous protein, Bat2p, of 376 amino acid residues was found in the cytosol. Both Bat protein s show striking similarity to the mammalian protein Eca39, which is on e of the few known targets of the myc oncogene, Deletion of a single B AT gene did not impair growth of yeast cells, In contrast, deletion of both genes resulted in an auxotrophy for branched chain amino acids ( Ile, Leu, and Val) and in a severe growth reduction on glucose-contain ing media, even after supply of these amino acids, Mitochondria and cy tosol isolated from bat1 and bat2 deletion mutants, respectively, cont ained largely reduced activities for the conversion of branched-chain 2-ketoacids to their corresponding amino acids, Thus, the Bat proteins represent the first known isoforms of yeast branched-chain amino acid transaminases. The severe growth defect of the double deletion mutant observed even in the presence of branched-chain amino acids suggests that the Bat proteins, in addition to the supply of these amino acids, perform another important function in the cell.