Centro de Envejecimiento y Regeneración (CARE UC); Departamento de Biología Celular y Molecular; Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile.
Mol Neurobiol. 2018 Dec;55(12):8965-8977. doi: 10.1007/s12035-018-1034-8. Epub 2018 Apr 4.
Mitochondria are widely recognized as fundamental organelles for cellular physiology and constitute the main energy source for different cellular processes. The location, morphology, and interactions of mitochondria with other organelles, such as the endoplasmic reticulum (ER), have emerged as critical events capable of determining cellular fate. Mitochondria-related functions have proven particularly relevant in neurons; mitochondria are necessary for proper neuronal morphogenesis and the highly energy-demanding synaptic transmission process. Mitochondrial health depends on balanced fusion-fission events, termed mitochondrial dynamics, to repair damaged organelles and/or improve the quality of mitochondrial function, ATP production, calcium homeostasis, and apoptosis, which represent some mitochondrial functions closely related to mitochondrial dynamics. Several neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases, have been correlated with severe mitochondrial dysfunction. In this regard, nicotine, which has been associated with relevant neuroprotective effects mainly through activation of the nicotinic acetylcholine receptor (nAChR), exerts its effects at least in part by acting directly on mitochondrial physiology and morphology. Additionally, a recent description of mitochondrial nAChR localization suggests a nicotine-dependent mitochondrial function. In the present work, we evaluated in cultured hipocampal neurons the effects of nicotine on mitochondrial dynamics by assessing mitochondrial morphology, membrane potential, as well as interactions between mitochondria, cytoskeleton and IPR, levels of the cofactor PGC-1α, and fission-fusion-related proteins. Our results suggest that nicotine modulates mitochondrial dynamics and influences mitochondrial association from microtubules, increasing IP receptor clustering showing modulation between mitochondria-ER communications, together with the increase of mitochondrial biogenesis.
线粒体被广泛认为是细胞生理学的基本细胞器，是不同细胞过程的主要能量来源。线粒体的位置、形态以及与内质网（ER）等其他细胞器的相互作用，已成为决定细胞命运的关键事件。线粒体相关功能在神经元中尤为重要；线粒体对于神经元的正常形态发生和高度耗能的突触传递过程是必需的。线粒体的健康依赖于平衡的融合-分裂事件，称为线粒体动力学，以修复受损的细胞器和/或改善线粒体功能、ATP 产生、钙稳态和细胞凋亡的质量，这些都是与线粒体动力学密切相关的线粒体功能。几种神经退行性疾病，如阿尔茨海默病、帕金森病和亨廷顿病，都与严重的线粒体功能障碍有关。在这方面，尼古丁通过激活烟碱型乙酰胆碱受体（nAChR）与相关的神经保护作用有关，至少部分通过直接作用于线粒体生理学和形态发挥其作用。此外，最近对线粒体 nAChR 定位的描述表明，线粒体功能依赖于尼古丁。在本工作中，我们通过评估线粒体形态、膜电位以及线粒体与细胞骨架和 IP 受体（IPR）之间的相互作用、辅助因子 PGC-1α 的水平以及分裂-融合相关蛋白，在培养的海马神经元中评估了尼古丁对线粒体动力学的影响。我们的结果表明，尼古丁调节线粒体动力学，并影响线粒体与微管的结合，增加 IP 受体聚集，显示出线粒体-内质网通讯之间的调节，同时增加线粒体生物发生。
