Transcellular degradation of axonal mitochondria
Transcellular degradation of axonal mitochondria
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DOI：
10.1073/pnas.1404651111
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发表时间：
2014-07-01
影响因子：
11.1
通讯作者：
Marsh-Armstrong, Nicholas
中科院分区：
文献类型：
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作者：
Davis, Chung-ha O.;Kim, Keun-Young;Marsh-Armstrong, Nicholas
人们普遍认为，健康细胞会降解自身的线粒体。在这里，我们报道了WT小鼠的视网膜神经节细胞轴突在视神经头（ONH）脱落线粒体，并且这些线粒体被邻近的星形胶质细胞内化和降解。电镜显示，线粒体通过源自健康轴突的大突起而脱落。一种病毒引入的酸化线粒体串联荧光蛋白报告显示，来自视网膜神经节细胞的酸化轴突线粒体与ONH星形胶质细胞柱内的溶酶体有关。据记者报道，ONH处视网膜神经节细胞线粒体的降解比例大于神经节细胞体。一致地，对降解DNA的分析显示视神经星形胶质细胞内广泛的mtDNA降解，其中一些来自视网膜神经节细胞轴突。总之，这些结果表明，视网膜神经节细胞轴突线粒体的惊人比例通常被ONH的星形胶质细胞降解。这种线粒体的跨细胞降解或自噬可能发生在中枢神经系统的其他地方，因为在大脑皮层的浅层神经突上也发现了结构上类似的降解线粒体的积累。因此，关于神经元或其他细胞必须降解自身线粒体的普遍假设应该重新考虑。
It is generally accepted that healthy cells degrade their own mitochondria. Here, we report that retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and that these mitochondria are internalized and degraded by adjacent astrocytes. EM demonstrates that mitochondria are shed through formation of large protrusions that originate from otherwise healthy axons. A virally introduced tandem fluorophore protein reporter of acidified mitochondria reveals that acidified axonal mitochondria originating from the retinal ganglion cell are associated with lysosomes within columns of astrocytes in the ONH. According to this reporter, a greater proportion of retinal ganglion cell mitochondria are degraded at the ONH than in the ganglion cell soma. Consistently, analyses of degrading DNA reveal extensive mtDNA degradation within the optic nerve astrocytes, some of which comes from retinal ganglion cell axons. Together, these results demonstrate that surprisingly large proportions of retinal ganglion cell axonal mitochondria are normally degraded by the astrocytes of the ONH. This transcellular degradation of mitochondria, or transmitophagy, likely occurs elsewhere in the CNS, because structurally similar accumulations of degrading mitochondria are also found along neurites in superficial layers of the cerebral cortex. Thus, the general assumption that neurons or other cells necessarily degrade their own mitochondria should be reconsidered.