CARBOXYMETHYLATED PHOSPHATIDYLETHANOLAMINE IN MITOCHONDRIAL-MEMBRANESOF MAMMALS - EVIDENCE FOR INTRACELLULAR LIPID GLYCOXIDATION

The non-enzymatic modification of aminophospholipids with lipoperoxida tion-derived aldehydes and glycoxidation-derived products have been re ported previously. However, it remains unknown whether intracellular m embranes are damaged by these glycoxidation-derived products. To inves tigate this issue, we tested whether aminophospholipids from mitochond rial membranes are damaged by glycoxidative stress the mitochondrion b eing identified as the major site of reactive-species production in th e cell. We have used a on-monitoring/gas-chromatography/mass-spectrome try assay for carboxymethylethanolamine (CM-Etn) detection, and provid e evidence for the presence of CM-Etn in mitochondrial phospholipids. Further, as a physiological approach to evaluate the influence of mito chondrial oxidative stress in CM-Etn formation, we also present the co mparative levels of CM-Etn in mitochondrial membranes of ten mammalian species ranging in maximum life-span from 3.5 years to 100, since the rate of mitochondrial reactive-oxygen-species production is inversely correlated to the maximum life-span. Our results show that CM-Etn lev els correlate in a logarithmic fashion with the maximum-life-span {[CM -Etn] = 0.51 + 0.50 x', where x' = log (maximum-life-span); r = 0.81, P < 0.004). The data demonstrate the intracellular ocurrence of glycox idative processes affecting membrane lipids. Moreover, these data show that longer-lived mammals contain higher levels of CM-Etn in mitochon drial membrane aminophospholipids. This trend could result from differ ences in rates of CM-Etn accumulation and/or phospholipid turnover.