THE PEPTIDE MASTOPARAN IS A POTENT FACILITATOR OF THE MITOCHONDRIAL PERMEABILITY TRANSITION
THE PEPTIDE MASTOPARAN IS A POTENT FACILITATOR OF THE MITOCHONDRIAL PERMEABILITY TRANSITION
复制标题
DOI：
10.1074/jbc.270.9.4923
复制
发表时间：
1995-03-03
影响因子：
4.8
通讯作者：
ERDAHL, WL
中科院分区：
文献类型：
--
作者：
PFEIFFER, DR;GUDZ, TI;ERDAHL, WL
Mastoparan通过明显的双峰作用机制促进线粒体渗透性转换孔的打开。在亚微摩尔浓度范围内，Mastoparan的作用依赖于介质Ca 2+和磷酸盐浓度，并受到环孢菌素A的抑制。在高于1 μ M的浓度下，Mastoparan诱导孔发生而不需要明显的Ca 2+，并且以环孢菌素A不敏感的方式，利用磷脂囊泡的研究表明，mastoparan通过强烈依赖于跨膜电位的机制在两个浓度范围内扰动双层膜。然而，溶质尺寸排阻研究表明，响应于低和高浓度的mastoparan在线粒体中形成的孔是渗透性转换孔。提出低浓度的mastoparan影响孔本身，更高的浓度具有通过对脂质相施加的作用使线粒体内膜去极化的额外效果。这可能是这些作用的组合，其允许在不存在Ca 2+和存在环孢菌素A的情况下孔开放，尽管其他解释仍然可行。mastoparan及其类似物MP 14对线粒体和磷脂囊泡的活性的比较提供了G蛋白可能参与渗透性转换孔的调节的初步指示。这些研究引起了对肽的注意，在广义上，在生理和病理条件下，作为细胞中潜在的孔调节剂。
Mastoparan facilitates opening of the mitochondrial permeability transition pore through an apparent bimodal mechanism of action, In the submicromolar concentration range, the action of mastoparan is dependent upon the medium Ca2+ and phosphate concentration and is subject to inhibition by cyclosporin A, At concentrations above 1 mu M, pore induction by mastoparan occurs without an apparent Ca2+ requirement and in a cyclosporin A insensitive manner, Studies utilizing phospholipid vesicles show that mastoparan perturbs bilayer membranes across both concentration ranges, through a mechanism which is strongly dependent upon transmembrane potential, However, solute size exclusion studies suggest that the pores formed in mitochondria in response to both low and high concentrations of mastoparan are the permeability transition pore, It is proposed that low concentrations of mastoparan influence the pore per se, with higher concentrations having the additional effect of depolarizing the mitochondrial inner membrane through an action exerted upon the lipid phase. It may be the combination of these effects which allow pore opening in the absence of Ca2+ and in the presence of cyclosporin A, although other interpretations remain viable, A comparison of the activities of mastoparan and its analog, MP14, on mitochondria and phospholipid vesicles provides an initial indication that a G-protein may participate in regulation of the permeability transition pore, These studies draw attention to peptides, in a broad sense, as potential pore regulators in cells, under both physiological and pathological conditions.