RELEASE OF GROUP IIA SECRETORY PHOSPHOLIPASE A2 FROM RAT BRAIN MITOCHONDRIA: DOES IT CORRELATE WITH THAT OF CYTOCHROME c?

Different secretory PLA2 (sPLA2) have been identified in brain tissue but the role of each enzyme is far for being clearly definite (Farooqui et al. J. Neurochem. 69:889, 1997). It has been proposed that their acti- vation might contribute to cell damage and that are likely linked to necrotic and/or apoptotic cell death. The presence of group IIA sPLA2 (GIIA) in the inner mitochondrial membrane and the release of the enzyme under reduced membrane potential (Macchioni, L. et al., J. Biol. Chem. 279:37860, 2004) induced to speculate on the mechanism of release and the possible correlation with cytochrome c (cyt c) release. We have previously demonstrated that potassium phosphate (Pi) at concentration producing mitochondrial permeability transition pore (mPTP) opening, did not affect GIIA release. The same effect was observed when mitochondria were exposed to Ca2+, a mPTP inducer, at concentration of 0–100mM. We also evaluated the effect of cyclosporine A (CsA), a potent inhibitor of mPTP pores that partially prevent mitochondrial swelling from brain tissue (Kobayashi, T. et al., Brain Res. 960:62, 2003); CsA did not affect the GIIA release. These findings strongly suggest that the release of GIIA may occur via an mPTP-independent mechanism and the effects of Pi, Ca2+ and CsA were the same observed for cyt c release. GIIA release was inhibited in cardiolipin (CL)-enriched mitochondria as observed for cyt c release (Piccotti, L. et al. J. Biol. Chem. 277:12075, 2002). These data sug- gests a possible correlation between mitochondrial GIIA and cyt c release and induces to speculate on the role of the enzyme in cellular life or death.