Mari State University, pl. Lenina 1, Yoshkar-Ola, Mari El, 424001, Russia.
Institute of Cell Biophysics, Russian Academy of Sciences, ul. Institutskaya 3, Pushchino, Moscow region, 142290, Russia.
J Bioenerg Biomembr. 2018 Oct;50(5):391-401. doi: 10.1007/s10863-018-9771-y. Epub 2018 Sep 5.
The paper examines membranotropic Ca-dependent effects of ω-hydroxypalmitic acid (HPA), a product of ω-oxidation of fatty acids, on the isolated rat liver mitochondria and artificial membrane systems (liposomes). It was established that in the presence of Ca, HPA induced aggregation of liver mitochondria, which was accompanied by the release of cytochrome c from the organelles. It was further demonstrated that the addition of Ca to HPA-containing liposomes induced their aggregation and/or fusion. Ca also caused the release of the fluorescent dye sulforhodamine B from liposomes, indicating their permeabilization. HPA was shown to induce a high-amplitude swelling of Ca-loaded mitochondria, to decrease their membrane potential, to induce the release of Ca from the organelles and to result in the oxidation of the mitochondrial NAD(P)H pool. Those effects of HPA were not blocked by the MPT pore inhibitor CsA, but were suppressed by the mitochondrial calcium uniporter inhibitor ruthenium red. The effects of HPA were also observed when Ca was replaced with Sr (but not with Ba or Mg). A supposition is made that HPA can induce a Ca-dependent aggregation of mitochondria, as well as Cadependent CsA-insensitive permeabilization of the inner mitochondrial membrane - with the subsequent lysis of the organelles.
本文研究了ω-氧化脂肪酸产物ω-羟棕榈酸(HPA)对分离的大鼠肝线粒体和人工膜系统(脂质体)的膜转导 Ca 依赖性效应。结果表明,在 Ca 存在的情况下,HPA 诱导肝线粒体聚集,伴随着细胞色素 c 从细胞器释放。进一步证明,向含有 HPA 的脂质体中添加 Ca 会诱导它们聚集和/或融合。Ca 还导致荧光染料 sulforhodamine B 从脂质体中释放,表明其通透性增加。HPA 诱导 Ca 负载的线粒体发生高幅度肿胀,降低其膜电位,诱导细胞器内 Ca 释放,并导致线粒体 NAD(P)H 池氧化。这些 HPA 效应不受 MPT 孔抑制剂 CsA 阻断,但被线粒体钙单向转运体抑制剂钌红抑制。当用 Sr(而不是 Ba 或 Mg)代替 Ca 时,也观察到 HPA 的作用。假设 HPA 可以诱导 Ca 依赖性的线粒体聚集,以及 Ca 依赖性的 CsA 不敏感的线粒体内膜通透性增加,随后导致细胞器溶解。