Lapidus R G, Sokolove P M
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
Arch Biochem Biophys. 1993 Oct;306(1):246-53. doi: 10.1006/abbi.1993.1507.
Mitochondria that have accumulated Ca2+ can be induced to undergo a permeability transition: the inner membrane becomes nonselectively permeable to small (< 1500 Da) solutes. The molecular mechanism(s) underlying this transition, which is Ca(2+)-dependent and cyclosporin A-sensitive, has yet to be clearly elucidated. Our laboratory has recently identified the polyamine spermine as an inhibitor of the permeability transition of isolated rat heart mitochondria. In this study, we have used spermine, in combination with a series of triggering agents, to clarify several mechanistic details of the transition process in isolated rat liver mitochondria. Mitochondrial swelling was monitored as an indicator of transition occurrence. Our results indicate that: (1) spermine inhibits the permeability transition of isolated rat liver mitochondria; (2) the sensitivity of the permeability transition of liver mitochondria to spermine is highly dependent on the ionic composition of the assay medium; (3) K+ interacts with a site outside the mitochondria to decrease spermine effectiveness; (4) spermine likewise acts at an external site; and (5) the Ca2+ uniporter in its inactive form is not the protein responsible for mediating the permeability transition.
内膜对小分子（<1500道尔顿）溶质变得非选择性通透。这种转变依赖钙离子且对环孢素A敏感，其潜在的分子机制尚未完全阐明。我们实验室最近发现多胺精胺是分离的大鼠心脏线粒体通透性转变的抑制剂。在本研究中，我们使用精胺与一系列触发剂相结合，以阐明分离的大鼠肝脏线粒体转变过程的几个机制细节。监测线粒体肿胀作为转变发生的指标。我们的结果表明：（1）精胺抑制分离的大鼠肝脏线粒体的通透性转变；（2）肝脏线粒体通透性转变对精胺的敏感性高度依赖于测定介质的离子组成；（3）钾离子在线粒体外与一个位点相互作用以降低精胺的有效性；（4）精胺同样作用于外部位点；（5）无活性形式的钙离子单向转运体不是负责介导通透性转变的蛋白质。
