Mitochondrial iPLA2 activity modulates the release of cytochrome c from mitochondria and influences the permeability transition
Mitochondrial iPLA2 activity modulates the release of cytochrome c from mitochondria and influences the permeability transition
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DOI：
10.1074/jbc.m510845200
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发表时间：
2006-03-17
影响因子：
4.8
通讯作者：
Pfeiffer, DR
中科院分区：
文献类型：
--
作者：
Gadd, ME;Broekemeier, KM;Pfeiffer, DR
线粒体钙非依赖性磷脂酶A(2)在膜电位持续下降的条件下，在能量依赖性的钙积累过程中被激活。这种激活并不依赖于线粒体通透性转变的诱导。抑制磷脂酶的溴烯醇内酯是一种有效的过渡抑制剂，这种作用可以被低水平的外源游离脂肪酸所克服。显然，钙非依赖性磷脂酶的激活是去极化和钙离子积累促进通透性转换孔开放的机制中的一个因素。钙非依赖性磷脂酶A(2)的持续活性促进了线粒体外膜的破裂和细胞色素c的自发释放，其时间尺度类似于细胞中发生的凋亡。然而，与酶被抑制时相比，当酶活性时，必须发生更多的基质空间膨胀，以刺激给定的细胞色素C组分的释放。线粒体钙非依赖性磷脂酶A(2)通过影响膜间隙蛋白的通透性转换和释放，可能是导致细胞死亡的重要因素。
The mitochondrial Ca2+-independent phospholipase A(2) is activated during energy-dependent Ca2+ 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 Ca2+-independent phospholipase is a factor in the mechanisms by which depolarization and Ca2+ accumulation promote opening of the permeability transition pore. Sustained activity of the Ca2+-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 Ca2+-independent phospholipase A(2) may be an important factor governing cell death caused by necrosis or apoptosis.