The fatty acid (FA) composition of mammalian cell membranes is highly regulated. Examples of large scale acyl modifications of phospholipid pools are few, and as a result, the roles of specific FAs on membrane function are poorly understood. Here we describe an extensive acyl modification of cardiolipin, a phospholipid found exclusively in the inner mitochondria! membrane. Cardiolipin (CL) is found to be associated with cytochrome c oxidase, which requires the lipid for activity. To determine the selectivity of cardiolipin for various FAs, 50% confluent HT-29 cells were treated with 50 uM exogenous DHA, linoleate, oleate and eicosapentaenoic acid (EPA) for 72 hours. All cells were cultured in the presence of 10% fetal calf serum. FA analysis of the lipids revealed that exogenous DHA and linoleate are extensively incorporated into CL, while oleate and EPA are only moderately enriched. Additionally, DHA is not enriched in CL from cells treated exogenously with precursor (EPA). Extending the treatment time did not increase the DHA content above 50%, suggesting either a positional or functional limitation to further Incorporation. Fatty acid composition (%wt.+/-S.D.) of CL treated with 50 urn exogenous fatty acid Control Oleate Linoleate EPA DHA 18:0 7.2 ±2.7 26.3±3.0 8.4± 0.5 4.8± 1.8 6.010.2 18:2 5.4± 1.2 6.4± 0.8 41.3±5.3 1.8±0.5 1.6±0.1 20:5 0.4±0.6 - - 14.2±0.2 1.1±0.1 22:6 0.7±1.2 0.3 ± 0.2 1.6 ± 0.9 1.3±0.1 47.2±0.2 The replacement of nearly 50% of the FA content of CL suggests a striking selectivity for DHA. It also profoundly modifies the structure and potentially the function of the inner mitochondria! membrane. This large increase in the DHA content of a lipid which is tightly associated with oxidative enzymes could produce a significant oxidant challenge for the cell. Mitochondria! pxidant stress is found to modulate enzymatic antioxidant activity as well as induce cell death. The selective incorporation of DHA into cardiolipin offers a possible mechanism for the modulation of apoptotic death rates of cells In animals fed diets containing fish oil.
|Original language||English (US)|
|State||Published - 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology