A comparison of phospholipid degradation by oxidation and hydrolysis during the mitochondrial permeability transition.

The peroxidation and hydrolysis of mitochondrial phospholipids has been examined under conditions which are referable to induction of the permeability transition by t-butylhydroperoxide. Over a 30-min time course, the peroxide causes formation of 0.3 nmol/mg protein of malondialdehyde. This value is little effected by Ca2+, Sr2+, or Mn2+ but is increased approximately fivefold by Fe2+. The latter cation, but not the others, results in malondialdehyde formation in the absence of added peroxide. Partially oxidized phosphatidylethanolamine is present in normal mitochondria and is increased by approximately 50% following t-butylhydroperoxide treatment; however, the amounts observed are in the range of 0.4-0.6 mol% of total phosphatidylethanolamine. The minor degradation by peroxidation is in contrast to approximately 2.5 mol% degradation which occurs by hydrolysis. This degree of hydrolysis is accompanied by mitochondrial swelling and Mg2+ release, while a comparable level of peroxidation (malondialdehyde formation) is not. It is concluded that induction of the permeability transition by t-butylhydroperoxide does not represent damage to the membrane lipid phase caused by peroxidation. It is possible, however, that peroxidation accelerates the accumulation of phospholipid hydrolysis products and is thereby a factor which favors the transition.