The mechanism of cardiolipin biosynthesis in liver mitochondria

Abstract

1. 1. When added exogenously, both CDP- and dCDP-diglyceride supported diphosphatidylglycerol synthesis from phosphatidyl[1'-14C] glycerol in intact mitochondria. The maximum rate observed for CDP-diglyceride was about 2-fold greater than for dCDP-diglyceride. At optimal concentrations of CDP-diglyceride a 30-fold stimulation of diphosphatidylglycerol synthesis was observed.

2. 2. [14C] Glycerol was not formed in significant amounts during mitochondrial conversion of phosphatidyl[1'-14C] glycerol to diphosphatidylglycerol.

3. 3. In mitochondria, [2-3H]phosphatidyl[1'-14C] glycerol was converted in the presence of unlabeled CDP-diglyceride to a diphosphatidylglycerol having a nearly identical 3H/14C ratio. The above evidence confirms that diphosphatidylglycerol is formed from phosphatidylglycerol and CDP-diglyceride in mitochondria.

4. 4. In contrast, in preparations of membranes from Escherichia coli K12, the diphosphatidylglycerol formed at low concentrations of CDP-diglyceride had a 3H/14C ratio of 2.0 relative to its precursor [2-3H]phosphatidyl[1'-14C] glycerol. Furthermore, significant amounts of [14C] glycerol were isolated after incubation of the E. coli membranes with phosphatidyl[1'-14C]glycerol. These findings indicate that in E. coli diphosphatidylglycerol is formed from two molecules of phosphatidylglycerol. However, evidence is presented which suggests the operation of the CDP-diglyceride pathway in E. coli at higher concentrations of CDP-diglyceride.