KINETIC EVIDENCE FOR A HEART MITOCHONDRIAL PORE ACTIVATED BY CA-2+, INORGANIC-PHOSPHATE AND OXIDATIVE STRESS - A POTENTIAL MECHANISM FOR MITOCHONDRIAL DYSFUNCTION DURING CELLULAR CA-2+ OVERLOAD
KINETIC EVIDENCE FOR A HEART MITOCHONDRIAL PORE ACTIVATED BY CA-2+, INORGANIC-PHOSPHATE AND OXIDATIVE STRESS - A POTENTIAL MECHANISM FOR MITOCHONDRIAL DYSFUNCTION DURING CELLULAR CA-2+ OVERLOAD
复制标题
DOI：
10.1111/j.1432-1033.1988.tb14475.x
复制
发表时间：
1988-12-15
期刊：
影响因子：
--
通讯作者：
COSTI, A
中科院分区：
文献类型：
--
作者：
CROMPTON, M;COSTI, A
已经进一步研究了Ca 2+诱导的线粒体透化作用可归因于可逆的Ca 2+活化孔的证据[Al Nasser和Crompton（1986）Biochem.J.239，19-29]。透化是由Ca 2+加磷酸盐或Ca 2+加叔丁基氢过氧化物以完全协同的方式诱导的。当透化完成时，线粒体外[14 C]蔗糖与基质空间平衡的半衰期约为800 ms; [14 C]甘露醇的平衡速度至少快三倍。当[14 C]蔗糖平衡的半衰期增加600-1400倍（至550- 1150 s）时，透化作用在用EGTA螯合Ca 2+时基本上完全逆转。脉冲流[14 C]溶质包埋技术已被开发来测量EGTA诱导的再密封的动力学。该技术结合了一个合适的选择[14 C]溶质和一个适当的数据分析模型，并有能力测量渗透状态的变化发生在100毫秒。所获得的数据是一致的指数resealing线粒体中的任何一个单一的mitochondira孔关闭高度的同步性。ADP使再密封速率增加约8倍（半衰期约为100分钟）。1 s; Km近似30 *MM）。CoA、Mg 2+、AMP和ATP，当考虑到水解产生的ADP时，基本上是无效的。它的结论是，心脏线粒体确实包含一个孔，其渗透状态控制在约1000倍的范围内由Ca 2+和其他因素，包括磷酸盐，氧化应激和ADP。本文还讨论了该孔在心脏再氧损伤中的可能作用。
Evidence that the Ca2+-induced permeabilization of mitochondria is attributable to a reverisble Ca2+-activated pore [Al Nasser and Crompton (1986) Biochem. J. 239, 19-29] has been further investigated. Permeabilization is induced in a wholly synergistic manner by either Ca2+ plus phosphate or Ca2+ plus tert-butyl hydroperoxide. When permeabilization is complete, extramitochondrial [14C]sucrose equilibrates with the matrix space with a half-time of about 800 ms; [14C]mannitol equilibrates at least threefold faster. Permeabilization is essentially fully reversed on Ca2+ chelation with EGTA, when the half time for [14C]sucrose equilibration is increased 600-1400-fold (to 550-1150s). A pulsed-flow [14C]solute-entrapment technique had been developed to measure the kinetics of EGTA-induced resealing. The technique incorporates a suitable choice of [14C]solute and an appropriate model for data analysis, and is competent to measure permeation state changes occurring in 100ms. The data obtained are consistent with exponential resealing of mitochondria in which pores of any single mitochondira close with a high degree of synchrony. The rate of resealing is increased about eight-fold by ADP (half-time .apprxeq. 1 s; Km .apprxeq. 30 *MM). CoA, Mg2+, AMP and also ATP, when account is taken of ADP arising by hydrolysis, are essentially ineffective. It is concluded that heart mitochondria do contain a pore whose permeation state is controlled over an approximate 1000-fold range by Ca2+ and other factors including phosphate, oxidative stress and ADP. The possible involvement of the pore in reoxygenation-induced injury in heart is discussed.