Transport of Ca2+ and Ca2+-Dependent Permeability Transition in Rat Liver Mitochondria under the Streptozotocin-Induced Type I Diabetes
Transport of Ca2+ and Ca2+-Dependent Permeability Transition in Rat Liver Mitochondria under the Streptozotocin-Induced Type I Diabetes
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DOI：
10.3390/cells8091014
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发表时间：
2019-09-01
期刊：
影响因子：
6
通讯作者：
Belosludtseva, Natalia, V
中科院分区：
文献类型：
--
作者：
Belosludtsev, Konstantin N.;Talanov, Eugeny Yu;Belosludtseva, Natalia, V
虽然糖尿病被认为是一种与线粒体功能障碍相关的疾病，但并不是所有的事情都是清楚的，线粒体钙离子转运和钙离子诱导的糖尿病细胞通透性转变。本工作的目的是研究链脲佐菌素诱导的I型糖尿病大鼠肝细胞内MCU的运作和钙离子依赖的线粒体通透性。结果表明，糖尿病动物诱导2周后，线粒体钙摄取速率增加约1.4倍。MCU和MICU1亚基的表达没有变化，但显性-负性MCUb通道亚基的数量几乎减少了一倍。细胞器对CsA敏感的MPT孔的诱导也变得更耐受，而对CsA不敏感的棕榈酸盐/钙离子诱导的孔的诱导则变得更不耐受。糖尿病肝细胞线粒体的膜脂基质也发生了变化。膜中的脂肪酸含量增加，脂双层的微粘度(用Laurdan法评估)增加。同时，脂质过氧化(通过丙二醛的产生来评估)被刺激。本文从细胞生理学的角度讨论了糖尿病引起的线粒体改变的后果。
Although diabetes mellitus is known to be a disease associated with mitochondrial dysfunction, not everything is clear about mitochondrial Ca2+ transport and Ca2+-induced permeability transition in diabetic cells. The objective of this work was to study the operation of MCU and Ca2+-dependent mitochondrial permeabilization in the liver cells of Sprague-Dawley rats under the streptozotocin-induced type I diabetes. It was shown that two weeks after the induction of diabetes, the rate of Ca2+ uptake by the mitochondria of diabetic animals increased similar to 1.4-fold. The expression of MCU and MICU1 subunits did not change, yet the quantity of dominant-negative MCUb channel subunits was almost twice as lower. The organelles also became more resistant to the induction of CsA-sensitive MPT pore and less resistant to the induction of CsA-insensitive palmitate/Ca2+-induced pore. The mitochondria of diabetic liver cells also showed changes in the lipid matrix of their membranes. The content of fatty acids in the membranes grew, and microviscosity of the lipid bilayer (assessed with laurdan) increased. At the same time, lipid peroxidation (assessed by the production of malonic dialdehyde) was stimulated. The paper discusses the consequences of the diabetes-related changes in mitochondria in the context of cell physiology.