Activation of liver mitochondrial phospholipase A2 by superoxide.

Mitochondrial damage is one of the prominent features of cell injury during oxidative stress and altered mitochondrial lipids may contribute to this damage. Lipid changes were observed when liver mitochondria were exposed to superoxide generating systems. Phosphatidylcholine and phosphatidylethanolamine contents were decreased with simultaneous formation of lysophospholipids when exposed to superoxide. Among the neutral lipids there was an increase in the level of free fatty acids. This alteration in lipid composition could be prevented by the simultaneous presence of superoxide dismutase or phospholipase A2 (PLA2) inhibitors. H2O2 did not have any effect on liver mitochondrial PLA2. This suggests that superoxide anion stimulates phospholipase A2 which is prevented by superoxide scavenging agents and PLA2 inhibitors. The products of phospholipase A2 are membrane-damaging agents which may be responsible for mitochondrial damage seen during oxidative stress.