CARDIOLIPIN SYNTHASE FROM YEAST

Cardiolipin synthase catalyzes the synthesis of the mitochondrial phos pholipid cardiolipin. Cardiolipin synthase is a unique membrane-bound enzyme in that it utilizes two phospholipids, both insoluble in water, as substrates. Kinetic analysis suggests that the enzyme forms a tern ary complex with the two lipid substrates, and that a divalent metal i on directly associates with cardiolipin synthase to form the active en zyme. While little is known about the regulation of cardiolipin syntha se in yeast, activity is reduced in mutants in which the mitochondrial genome is deleted, and in mutants with defective respiratory complexe s. In rho(0) mutants, which contain no mitochondrial DNA and are defec tive in the assembly of many mitochondrial membrane protein complexes, cardiolipin synthase activity is reduced by 50%. Mutants defective in respiratory complexes, particularly those incapable of cytochrome oxi dase assembly, also have reduced cardiolipin synthase activity. Thus i t is likely that respiration and cardiolipin formation are interdepend ent. The enzyme was recently purified from the budding yeast Saccharom yces cerevisiae. Enzyme activity was associated with a 25-30-kDa prote in. The amino acid sequence of this protein, combined with the availab ility of the complete yeast genome sequence, will hopefully lead to th e identification of the structural gene for this enzyme in the near fu ture. (C) 1997 Elsevier Science B.V.