ACN9 encodes a protein of the mitochondrial intermembrane space that is required for growth on acetate and other nonfermentable carbon sources (1, 3). Mutations in ACN9 lead to elevated levels of enzymes of the glyoxylate cycle, gluconeogenesis, and acetyl-CoA metabolism (1). Although the exact function of Acn9p is unknown, the protein is thought to be involved in gluconeogenesis as acn9 mutants share several phenotypes observed in mutants defective for gluconeogenic enzymes (2).

Gluconeogenesis is the process whereby glucose is synthesized from non-carbohydrate precursors, which enables yeast cells to grow on non-sugar carbon sources like ethanol, glycerol, or peptone. The reactions of gluconeogenesis, shown here, mediate conversion of pyruvate to glucose, which is the opposite of glycolysis, the formation of pyruvate from glucose. While these two pathways have several reactions in common, they are not the exact reverse of each other. As the glycolytic enzymes phosphofructokinase (Pfk1p, Pfk2p) and pyruvate kinase (Cdc19p) only function in the forward direction, the gluconeogenesis pathway replaces those steps with the enzymes pyruvate carboxylase (Pyc1p, Pyc2p) and phosphoenolpyruvate carboxykinase (Pck1p)-generating oxaloacetate as an intermediate from pyruvate to phosphoenolpyruvate-and also the enzyme fructose-1,6-bisphosphatase (Fbp1p) (reviewed in 4). Overall, the gluconeogenic reactions convert two molecules of pyruvate to a molecule of glucose, with the expenditure of six high-energy phosphate bonds, four from ATP and two from GTP.

ACN9 is expressed approximately 100-fold less than tricarboxylic acid and glyoxylate cycle genes and expression is only slightly repressed in the presence of glucose (3). Acn9p homologs have been identified in humans, nematodes, and mice (3).

Last updated: 2005-07-22