Palladin Institute of Biochemistry, 9, Leontovycha str., 01054 Kyiv, Ukraine.
Int J Biochem Cell Biol. 2022 Feb;143:106138. doi: 10.1016/j.biocel.2021.106138. Epub 2021 Dec 17.
Nicotinic acetylcholine receptors mediate fast synaptic transmission in neuro-muscular junctions and autonomic ganglia and modulate survival, proliferation and neurotransmitter or cytokine release in the brain and non-excitable cells. The neuronal-type nicotinic acetylcholine receptors are expressed in the outer mitochondria membrane to regulate the release of pro-apoptotic substances like cytochrome c or reactive oxygen species. In the intracellular environment, nicotinic acetylcholine receptor signaling is ion-independent and triggers intramitochondrial kinases, similar to those activated by plasma membrane nicotinic acetylcholine receptors. The present review will describe the data obtained during the last five years including, in particular, post-translational glycosylation as a targeting signal to mitochondria, mechanisms of mitochondrial nicotinic acetylcholine receptor signaling studied with subtype-specific agonists, antagonists, positive allosteric modulators and knockout mice lacking certain nicotinic acetylcholine receptor subunits, interaction of mitochondrial nicotinic acetylcholine receptors with Bcl-2 family proteins and their involvement in important pathologies like neuroinflammation, liver damage and SARS-CoV-2 infection.
烟碱型乙酰胆碱受体介导神经肌肉接头和自主神经节中的快速突触传递，并调节大脑和非兴奋细胞中的存活、增殖以及神经递质或细胞因子的释放。神经元型烟碱型乙酰胆碱受体表达在外线粒体膜上，以调节细胞色素 c 或活性氧等促凋亡物质的释放。在细胞内环境中，烟碱型乙酰胆碱受体信号是离子非依赖性的，并触发线粒体内激酶，类似于由质膜烟碱型乙酰胆碱受体激活的激酶。本综述将描述过去五年获得的数据，特别是包括翻译后糖基化作为靶向线粒体的信号、使用亚型特异性激动剂、拮抗剂、正变构调节剂和缺乏某些烟碱型乙酰胆碱受体亚单位的敲除小鼠研究的线粒体烟碱型乙酰胆碱受体信号转导机制、线粒体烟碱型乙酰胆碱受体与 Bcl-2 家族蛋白的相互作用及其在神经炎症、肝损伤和 SARS-CoV-2 感染等重要病理中的作用。
