Mitochondrial iPLA2 activity modulates the release of cytochrome c from mitochondria and influences the permeability transition.
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.
Gadd
Martha E
ME
Department of Molecular and Cellular Biochemistry, Ohio State University, 1645 Neil Avenue, Columbus, OH 43210, USA.
Broekemeier
Kimberly M
KM
Crouser
Elliott D
ED
Kumar
Jitendra
J
Graff
Gustav
G
Pfeiffer
Douglas R
DR
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism*; D054522:Group VI Phospholipases A2; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D008954:Models, Biological; D009336:Necrosis; D010101:Oxygen Consumption; D010539:Permeability; D010741:Phospholipases A / Q000737:chemistry / Q000378:metabolism*; D011189:Potassium Chloride / Q000737:chemistry; D051381:Rats; D013997:Time Factors
D003470:Culture Media; D011189:Potassium Chloride; D045304:Cytochromes c; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; D002118:Calcium