Cloning and characterization of the previously described Saccharomyces cerevisiae IMP) gene, which was assumed to be a nuclear determinant involved in the nucleomitochondrial control of the utilization of galactose, demonstrate allelism to the GAL2 gene. Galactose metabolism does not necessarily involve the induction of the specific transport system coded by GAL2/IMP1, because a null mutant takes up galactose and grows on it. Data on galactose uptake are presented, and the dependence on ATP for constitutive and inducible galactose transport is discussed. These results can account for the inability of impl/gal2 mutants to grow on galactose in a respiration-deficient background. Under these conditions, uptake was affected at the functional level but not at the biosynthetic level.In Saccharomyces cerevisiae, conversion of exogenous galactose to endogenous glucose 6-phosphate requires a galactose permease, encoded by the GAL2 gene, and the enzymes of the Leloir pathway (galactokinase, transferase, epimerase, and phopshoglucomutase, encoded by GAL1, GAL7, GAL10 and GAL5, respectively). The expression of these genes is coregulated; it is induced by galactose and repressed by glucose (14,22). The rapid response of induction is mediated by the activities of at least three trans-acting regulatory genes: GAL4, GAL80, and GAL3 (14). Moreover, glucose inactivates preexisting permease molecules, a process termed catabolite inactivation (12, 14).As originally claimed by Spiegelman (27), galactose utilization in some strains depends on mitochondrial function. The mitochondrial dependency appears to be mediated through the modulation of nuclear gene activity. In fact, (i) strains with mutations of either structural or regulatory genes (GAL1, GAL2, GAL3, GAL4, and GAL5) grow on galactose under respiration-sufficient (RS) conditions but not under respiration-deficient (RD) conditions (1, 9), and (ii) mitochondrial mutants derived from a number of strains that can grow and utilize galactose are unable to use this sugar (1,8,10,34). It has been suggested that gal3 and galS mutants can use galactose because proteins encoded by other genes share some function (GALl with GAL3 and PGMJ with GAL5) (3, 11). The relationship between alternative functions and the mitochondrial function remains to be established (2). Genetic analysis of the strain differences of the mitochondrial mutants indicates that mitochondrial changes alter the activity or expression of nuclear genes involved in the uptake and use of sugars (1,33).In particular, strains carrying the IMP1 allele can grow on and ferment galactose under both RS and RD conditions or in the presence of a mitochondrial inhibitor such as ethidium bromide or erythromycin. On the contrary, strains carrying the recessive allele impl can grow on and ferment galactose only under RS conditions. In the presence of ethidium bromide, galactose uptake and fermentation are blocked in impl mutants, indicating that the impl mutation makes galactose uptake dependent upon mitochondrial function (1).In an a...