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.

中文翻译：

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通过消耗饥饿反应因子 Ataxin-2 有效预防神经退行性疾病

Ataxin-2 (ATXN2) 同系物存在于所有真核生物中，并且可能促成了它们的起源。除了在内吞作用之外，它们还以对 mRNA 修复和核糖体翻译的整体影响而闻名。ATXN2 通过 mTORC1 信号传导抑制细胞大小、蛋白质合成以及脂肪和糖原储存。然而，特定的肝线粒体基质酶和线粒体修复因子 PINK1 需要 ATXN2 丰度。在饥饿期间，ATXN2 被转录诱导并定位于细胞质应力颗粒，在那里核因子停靠以补偿 RNA 病理。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 ATXN2 耗竭在预防运动神经元和小脑萎缩方面出奇地有效，如小鼠模型、果蝇和酵母所示。