CARDIOLIPIN SYNTHASE FROM MAMMALIAN MITOCHONDRIA

Cardiolipin was first isolated from beef heart and was shown to contai n an unusually high content of linoleic acid ester residues. Cardiolip in is found throughout the eukaryotes including animals, plants and fu ngi. In mammalian tissue and in yeast, cardiolipin is found exclusivel y in mitochondria. Mitochondrial synthesis of cardiolipin utilizes pho sphatidylglycerol and CDP-diacylglycerol as substrates in a reaction w hich requires a divalent cation (Mg2+, Mn2+ or Co2+). Cardiolipin synt hase has been purified to near-homogeneity from rat liver by solubiliz ation with Zwittergent 3-14 followed by FPLC anion exchange, gel perme ation and chromatofocusing steps. Cardiolipin synthase has a molecular mass of 50 kDa, a pH optimum of 8.0, and requires added phospholipids (phosphatidylethanolamine and cardiolipin) and 4 mM Co2+ for optimal activity. Except for the effects of divalent cations and the requireme nt for phospholipids, little is known about the regulation of cardioli pin synthase. Cardiolipin deficiency in aging mitochondria has been li nked to decreased metabolite transport across the inner membrane. Both cardiolipin levels and cardiolipin synthase activity are increased in hyperthyroidism and decreased in hypothyroidism suggesting regulation by thyroid hormone. Mammalian cardiolipin synthase has not been seque nced or cloned and its biological role in mitochondria is not yet full y understood. (C) 1997 Elsevier Science B.V.