Cardiolipin remodeling in a Chinese hamster lung fibroblast cell line deficient in oxidative energy production.
The metabolism of cardiolipin was investigated in a Chinese hamster lung fibroblast cell line CCL16-B2 deficient in oxidative energy metabolism and its parental cell line CCL16-B1. Mitochondrial enzyme activities involved in de novo cardiolipin biosynthesis were elevated in CCL16-B2 cells compared with CCL16-B1 cells, indicating initially an elevation in cardiolipin biosynthesis. Content of all phospholipids, including cardiolipin and its precursors, and high energy nucleotides were unaltered in CCL16-B2 cells compared to CCL16-B1 cells. When cells were incubated with [1,3-(3)H]glycerol for up to 4 h radioactivity incorporated into cardiolipin in CCL16-B2 cells did not differ compared with CCL16-B1 cells. In contrast, radioactivity incorporated into phosphatidylglycerol, the immediate precursor of cardiolipin, was elevated over 2-fold in CCL16-B2 cells compared with CCL16-B1 cells. Analysis of the fatty acid molecular species in cardiolipin revealed alterations in the level of unsaturated but not saturated fatty acids in B2 compared with B1 cells. In vivo cardiolipin remodeling, that is, the deacylation of cardiolipin to monolysocardiolipin followed by reacylation back to cardiolipin, with [1-(14)C]palmitate and [1-(14)C]oleate and in vitro mitochondrial phospholipid remodeling with [1-(14)C]linoleate were altered in CCL16-B2 cells compared to CCL16-B1 cells. Since both the appropriate content and molecular composition of cardiolipin is required for optimum mitochondrial oxidative phosphorylation, we suggest that the difference in CL molecular species composition observed in CCL16-B2 cells, mediated by alterations in in vivo cardiolipin remodeling, may be one of the underlying mechanisms for the reduction in oxidative energy production in CCL16-B2 cells.
Rusnak
A
A
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Mangat
R
R
Xu
F
F
McClarty
G
G
Hatch
G M
GM
D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D004734:Energy Metabolism; D005347:Fibroblasts / Q000378:metabolism; D019787:Linoleic Acid / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption
D002308:Cardiolipins; D019787:Linoleic Acid