Wu Zheng, Cardona Eric A, Cohn Jesse A, Pierce Jonathan T
Department of Neuroscience, Center for Learning and Memory, Waggoner Center for Alcohol & Addiction Research, University of Texas at Austin, Austin, TX 78712.
Proc Natl Acad Sci U S A. 2025 Jan 14;122(2):e2407909122. doi: 10.1073/pnas.2407909122. Epub 2025 Jan 9.
While traditionally studied for their proapoptotic functions in activating the caspase, research suggests BH3-only proteins also have other roles such as mitochondrial dynamics regulation. Here, we find that EGL-1, the BH3-only protein in , promotes the cell-autonomous production of exophers in adult neurons. Exophers are large, micron-scale vesicles that are ejected from the cell and contain cellular components such as mitochondria. EGL-1 facilitates exopher production potentially through regulation of mitochondrial dynamics. Moreover, an endogenous, low level of EGL-1 expression appears to benefit dendritic health. Our findings provide insights into the role of neuronal BH3-only protein in mitochondrial dynamics, downstream exopher production, and ultimately neuronal health.
虽然传统上对它们在激活半胱天冬酶方面的促凋亡功能进行了研究,但研究表明,仅含BH3结构域的蛋白质也具有其他作用,如线粒体动力学调节。在这里,我们发现秀丽隐杆线虫中的仅含BH3结构域的蛋白质EGL-1可促进成年神经元中外泌体的细胞自主产生。外泌体是从细胞中排出的大型微米级囊泡,含有线粒体等细胞成分。EGL-1可能通过调节线粒体动力学促进外泌体的产生。此外,内源性低水平的EGL-1表达似乎有利于树突健康。我们的研究结果为神经元中仅含BH3结构域的蛋白质在线粒体动力学、下游外泌体产生以及最终神经元健康中的作用提供了见解。