Interactions between mitochondria and endoplasmic reticulum in demyelinated axons
Interactions between mitochondria and endoplasmic reticulum in demyelinated axons
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DOI：
10.1007/s00795-018-0212-0
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发表时间：
2019-09-01
影响因子：
1.8
通讯作者：
Ohno, Nobuhiko
中科院分区：
文献类型：
--
作者：
Truc Quynh Thai;Huy Bang Nguyen;Ohno, Nobuhiko
脱髓鞘导致轴突变化，其涉及支持轴突代谢和存活的轴突线粒体的功能和动力学。然而，在脱髓鞘轴突中，线粒体和内质网之间的物理相互作用的变化，称为髓鞘相关膜，知之甚少。在这项研究中，我们研究了三维超微结构的变化，线粒体和内质网之间的轴突的慢性进行性脱髓鞘小鼠模型所造成的额外拷贝的蛋白脂质蛋白（PLP4e）的膜并列。在PLP4e小鼠的视神经中，大多数轴突在1月龄时被髓鞘包裹，但在5月龄时脱髓鞘。在1个月大时，PLP4e小鼠的线粒体比野生型小鼠的线粒体稍大，而并置的大小和频率相似。在5月龄时，PLP4e小鼠的线粒体大小和并置大小明显大于野生型小鼠。在脱髓鞘条件下的变性轴突中，线粒体的增大减少，而并置的密度和频率与非变性轴突相似。这些结果表明，线粒体和ER之间的相互作用在慢性脱髓鞘轴突增强，并保持在遗传性髓鞘疾病的轴突变性。
Demyelination leads to axonal changes that involve the functions and dynamics of axonal mitochondria supporting metabolism and survival of axons. However, the changes in the physical interactions between mitochondria and endoplasmic reticulum, called mitochondria-associated membranes, are poorly understood in demyelinated axons. In this study, we investigated the three-dimensional ultrastructural changes in membrane juxtapositions between mitochondria and endoplasmic reticulum in axons of a chronic progressive demyelination mouse model caused by extra copies of proteolipid protein (PLP4e). In the optic nerve of PLP4e mice, most axons were ensheathed by myelin by age 1 month, but were demyelinated by age 5 months. At age 1 month, mitochondria in PLP4e mice were slightly larger than those in wild-type mice, while the size and frequency of juxtaposition were similar. At age 5 months, the sizes of mitochondria and size of juxtaposition in PLP4e mice were prominently larger than those in wild-type mice. In degenerating axons under demyelination, the enlargement of mitochondria was diminished, while the density and frequency of juxtaposition were similar to those of non-degenerating axons. These results suggest that interactions between mitochondria and ER are enhanced in chronically demyelinated axons and maintained during axonal degeneration in hereditary myelin diseases.