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Systematic analysis of ribophagy in human cells reveals bystander flux during selective autophagy.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2018-Feb-01 , DOI: 10.1038/s41556-017-0007-x
Heeseon An , J. Wade Harper

Ribosomes are abundant cellular machines 1,2 that are regulated by assembly, supernumerary subunit turnover and nascent chain quality control mechanisms 1-5 . Moreover, nitrogen starvation in yeast has been reported to promote selective ribosome delivery to the vacuole in an autophagy conjugation system dependent manner, a process called 'ribophagy' 6,7 . However, whether ribophagy in mammals is selective or regulated is unclear. Using Ribo-Keima flux reporters, we find that starvation or mTOR inhibition promotes VPS34-dependent ribophagic flux, which, unlike yeast, is largely independent of ATG8 conjugation and occurs concomitantly with other cytosolic protein autophagic flux reporters 8,9 . Ribophagic flux was not induced upon inhibition of translational elongation or nascent chain uncoupling, but was induced in a comparatively selective manner under proteotoxic stress induced by arsenite 10 or chromosome mis-segregation 11 , dependent upon VPS34 and ATG8 conjugation. Unexpectedly, agents typically used to induce selective autophagy also promoted increased ribosome and cytosolic protein reporter flux, suggesting significant bulk or 'bystander' autophagy during what is often considered selective autophagy 12,13 . These results emphasize the importance of monitoring non-specific cargo flux when assessing selective autophagy pathways.

中文翻译:

对人体细胞中核糖核酸的系统分析揭示了选择性自噬过程中的旁观者通量。

核糖体是丰富的细胞机器1,2,受组装,多余的亚单位更新和新生链质量控制机制1-5的调节。此外,已报道酵母中的氮饥饿会以自噬结合系统依赖性方式促进选择性核糖体向液泡的传递,这一过程称为“核噬菌” 6,7。然而,尚不清楚哺乳动物的核糖核酸是选择性的还是可调节的。使用Ribo-Keima通量报告子,我们发现饥饿或mTOR抑制促进VPS34依赖性核糖通量,与酵母不同,它很大程度上独立于ATG8结合,并与其他胞质蛋白自噬通量报告子一起发生8,9。在抑制翻译伸长或新生链解偶联时,不能诱导核能通量,而是在由砷酸盐10或染色体错偏11引起的蛋白毒性胁迫下,以相对选择性的方式诱导,取决于VPS34和ATG8的结合。出乎意料的是,通常用于诱导选择性自噬的药物还促进了核糖体和胞浆蛋白报道分子通量的增加,表明在通常被认为是选择性自噬的过程中大量的“旁观者”自噬12,13。这些结果强调了在评估选择性自噬途径时监测非特异性货物通量的重要性。
更新日期:2017-12-11
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