Department of Neurology, Goethe University Medical School, 60590 Frankfurt am Main, Germany.
Department of Neurology, Goethe University Medical School, 60590 Frankfurt am Main, Germany.
Trends Neurosci. 2017 Aug;40(8):507-516. doi: 10.1016/j.tins.2017.06.004. Epub 2017 Jul 3.
Ataxin-2 (ATXN2) homologs exist in all eukaryotic organisms and may have contributed to their origin. Apart from a role in endocytosis, they are known for global effects on mRNA repair and ribosomal translation. Cell size, protein synthesis, and fat and glycogen storage are repressed by ATXN2 via mTORC1 signaling. However, specific liver mitochondrial matrix enzymes and the mitochondrial repair factor PINK1 require ATXN2 abundance. During periods of starvation, ATXN2 is transcriptionally induced and localized to cytosolic stress granules, where nuclear factors dock to compensate RNA pathology. These physiological actions were now revealed to be crucial for human neurodegenerative diseases, given that ATXN2 depletion is surprisingly efficient in preventing motor neuron and cerebellar atrophy, as demonstrated in mouse models, flies, and yeast.
在所有真核生物中都存在与共济失调蛋白 2（ATXN2）同源的蛋白，它们可能对真核生物的起源做出了贡献。除了在胞吞作用中的作用外，它们还以对 mRNA 修复和核糖体翻译的全局影响而闻名。ATXN2 通过 mTORC1 信号抑制细胞大小、蛋白质合成以及脂肪和糖原储存。然而，特定的肝脏线粒体基质酶和线粒体修复因子 PINK1 需要 ATXN2 的丰度。在饥饿期间，ATXN2 被转录诱导并定位于细胞质应激颗粒中，核因子在那里停靠以补偿 RNA 病理学。现在发现这些生理作用对人类神经退行性疾病至关重要，因为在小鼠模型、果蝇和酵母中，ATXN2 的耗竭可非常有效地预防运动神经元和小脑萎缩。
