Fernandes Maria A S, Jurado Amália S, Videira Romeu A, Santos Maria S, Moreno António J M, Velena Astrida, Duburs Gunars, Oliveira Catarina R, Vicente Joaquim A F
Departamento de Zoologia, Universidade de Coimbra, 3004-517 Coimbra, Portugal.
Mitochondrion. 2005 Oct;5(5):341-51. doi: 10.1016/j.mito.2005.06.004.
Considering that cerebrocrast stimulates oligomycin-inhibited state 3 respiration simultaneously with mitochondrial transmembrane potential (Deltapsi) dissipation, the mechanism underlying the uncoupler activity of cerebrocrast was assessed by its ability to permeabilize the mitochondrial inner membrane to H(+) or to K(+) or to cotransport anions with H(+). The partition coefficient of cerebrocrast in mitochondrial membrane and its ability to act as a membrane-active compound disturbing membrane lipid organization were also investigated. Cerebrocrast induced no permeabilization of mitochondrial inner membrane to H(+) or K(+), but it was able to transport H(+) in association with Cl(-). Cerebrocrast showed a strong incorporation into the mitochondrial membrane, with a partition coefficient (Kp(m/w)) of 2.7(+/-0.1)x10(5). Cerebrocrast also reduced, in a concentration dependent manner, the phase transition temperature, the cooperative unit size, and the enthalpy associated with the phase transition temperature of DMPC membrane bilayers. It was concluded that the uncoupler activity of cerebrocrast is due to its ability to promote the cotransport of H(+) with Cl(-) through the rat liver mitochondrial inner membrane, and that this cerebrocrast mechanism of action may be potentiated by alterations of membrane lipid organization and membrane lateral heterogeneity.
鉴于脑crast能在使线粒体跨膜电位（ΔΨ）耗散的同时刺激寡霉素抑制的状态3呼吸，通过其使线粒体内膜对H⁺、K⁺通透或与H⁺协同转运阴离子的能力来评估脑crast解偶联剂活性的潜在机制。还研究了脑crast在线粒体内膜中的分配系数及其作为干扰膜脂质组织的膜活性化合物的能力。脑crast未引起线粒体内膜对H⁺或K⁺的通透，但它能够与Cl⁻协同转运H⁺。脑crast在线粒体内膜中有很强的掺入能力，分配系数（Kp(m/w)）为2.7（±0.1）×10⁵。脑crast还以浓度依赖的方式降低了二肉豆蔻酰磷脂酰胆碱（DMPC）膜双层的相变温度、协同单元大小以及与相变温度相关的焓。得出的结论是，脑crast的解偶联剂活性归因于其促进H⁺与Cl⁻通过大鼠肝线粒体内膜协同转运的能力，并且这种脑crast的作用机制可能因膜脂质组织和膜侧向异质性的改变而增强。
