Acidosis promotes the permeability transition in energized mitochondria:: Implications for reperfusion injury
Acidosis promotes the permeability transition in energized mitochondria:: Implications for reperfusion injury
复制标题
DOI：
10.1089/08977150152693755
复制
发表时间：
2001-10-01
影响因子：
4.2
通讯作者：
Siesjö, BK
中科院分区：
文献类型：
--
作者：
Kristián, T;Bernardi, P;Siesjö, BK
我们研究了pH对失能和充能线粒体线粒体通透性转换孔(PTP)开放的影响。当着P-I的面。在失能的大鼠脑和心脏线粒体中，我们观察到在酸性pH值增加的情况下，钙离子诱导的PTP开放受到预期的抑制。出乎意料的是，用电子传递复合体I或复合体II底物供电的线粒体表现出相反的行为，酸性pH促进而不是抑制PTP开放。我们表明，酸性pH的增强作用是由于P-I吸收速率的增加。数据还显示，与心脏或肝脏线粒体相比，脑线粒体在通透性转变的开始方面具有更多的异质性，这种异质性取决于它们的P-I运输能力。综上所述，这些结果表明，酸性pH对PTP的抑制作用可以通过增加PI摄取率在原位被克服，而缺血和缺血后酸中毒可能加重而不是减轻PTP依赖的组织损伤。
We have studied the influence of pH on opening of the mitochondrial permeability transition pore (PTP) in both deenergized and energized mitochondria. in the presence of P-i. In deenergized mitochondria from rat brain and heart, we observed the expected inhibition of Ca2+-induced PTP opening at increasingly acidic pH values. Unexpectedly, mitochondria energized with either electron transport complex I or complex II substrates displayed the opposite behavior, acidic pH promoting rather than inhibiting PTP opening. We show that the potentiating effect of acidic pH is due to an increased rate of P-i uptake. The data also revealed that brain mitochondria are more heterogeneous than heart or liver mitochondria in relation to onset of a permeability transition, and that this heterogeneity depends on their P-i transport capacity. Taken together, these results indicate that the inhibitory effects of acidic pH on the PTP may be overcome in situ by an increased rate of Pi uptake, and that ischemic and postischemic acidosis may worsen rather than relieve PTP-dependent tissue damage.