Mitochondrial iPLA2 Activity Modulates the Release of Cytochrome c from Mitochondria and Influences the Permeability Transition

作者：Martha E. Gadd, Kimberly M. Broekemeier, Elliott D. Crouser, Jitendra Kumar, Gustav Graff, Douglas R. Pfeiffer · 发表于：Journal of Biological Chemistry · 年份：2006 · DOI：10.1074/jbc.m510845200 · 被引用次数：88 · 研究领域：Mitochondrial Function and Pathology、Metabolism and Genetic Disorders、ATP Synthase and ATPases Research

The mitochondrial Ca(2+)-independent phospholipase A(2) is activated during energy-dependent Ca(2+) accumulation under conditions where there is a sustained depression of the membrane potential. This activation is not dependent on induction of the mitochondrial permeability transition. Bromoenol lactone, which inhibits the phospholipase, is effective as an inhibitor of the transition, and this action can be overcome by low levels of exogenous free fatty acids. Apparently, activation of the Ca(2+)-independent phospholipase is a factor in the mechanisms by which depolarization and Ca(2+) accumulation promote opening of the permeability transition pore. Sustained activity of the Ca(2+)-independent phospholipase A(2) promotes rupture of the outer mitochondrial membrane and spontaneous release of cytochrome c on a time scale similar to that of apoptosis occurring in cells. However, more swelling of the matrix space must occur to provoke release of a given cytochrome c fraction when the enzyme is active, compared with when it is inhibited. Through its effects on the permeability transition and release of intermembrane space proteins, the mitochondrial Ca(2+)-independent phospholipase A(2) may be an important factor governing cell death caused by necrosis or apoptosis.