Byers Eye Institute and Spencer Center for Vision Research, Stanford University, Palo Alto, CA, 94303, USA.
University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
Sci Rep. 2019 Jul 23;9(1):10669. doi: 10.1038/s41598-019-46956-5.
The process of mitochondrial fission-fusion has been implicated in diverse neuronal roles including neuronal survival, axon degeneration, and axon regeneration. However, whether increased fission or fusion is beneficial for neuronal health and/or axonal growth is not entirely clear, and is likely situational and cell type-dependent. In searching for mitochondrial fission-fusion regulating proteins for improving axonal growth within the visual system, we uncover that mitochondrial fission process 1,18 kDa (MTP18/MTFP1), a pro-fission protein within the CNS, is critical to maintaining mitochondrial size and volume under normal and injury conditions, in retinal ganglion cells (RGCs). We demonstrate that MTP18's expression is regulated by transcription factors involved in axonal growth, Kruppel-like factor (KLF) transcription factors-7 and -9, and that knockdown of MTP18 promotes axon growth. This investigation exposes MTP18's previously unexplored role in regulating mitochondrial fission, implicates MTP18 as a downstream component of axon regenerative signaling, and ultimately lays the groundwork for investigations on the therapeutic efficacy of MTP18 expression suppression during CNS axon degenerative events.
线粒体裂变-融合过程与多种神经元功能有关，包括神经元存活、轴突退化和轴突再生。然而，增加裂变或融合是否有利于神经元健康和/或轴突生长尚不完全清楚，这可能与情况和细胞类型有关。在寻找线粒体裂变-融合调节蛋白以改善视觉系统中的轴突生长时，我们发现线粒体裂变过程 1,18 kDa（MTP18/MTFP1），中枢神经系统中的一种促裂变蛋白，对于维持正常和损伤条件下的视网膜神经节细胞（RGCs）中的线粒体大小和体积至关重要。我们证明了 MTP18 的表达受涉及轴突生长的转录因子调控，即 Krüppel 样因子（KLF）转录因子-7 和 -9，并且 MTP18 的敲低促进了轴突生长。这项研究揭示了 MTP18 在调节线粒体裂变中的先前未知作用，暗示 MTP18 是轴突再生信号的下游组成部分，最终为在中枢神经系统轴突退行性事件期间抑制 MTP18 表达的治疗效果的研究奠定了基础。
