Translation of mRNAs is tightly regulated and constantly surveyed for errors. Aberrant translation can trigger co-translational protein and RNA quality control processes, impairments of which cause neurodegeneration by still poorly understood mechanism(s). Here we show that quality control of translation of mitochondrial outer membrane (MOM)-localized mRNA intersects with the turnover of damaged mitochondria, both orchestrated by the mitochondrial kinase PINK1. Mitochondrial damage causes stalled translation of complex-I 30 kDa subunit (C-I30) mRNA on MOM, triggering the recruitment of co-translational quality control factors Pelo, ABCE1, and NOT4 to the ribosome/mRNA-ribonucleoprotein complex. Damage-induced ubiquitination of ABCE1 by NOT4 generates poly-ubiquitin signals that attract autophagy receptors to MOM to initiate mitophagy. In the Drosophila PINK1 model, these factors act synergistically to restore mitophagy and neuromuscular tissue integrity. Thus ribosome-associated co-translational quality control generates an early signal to trigger mitophagy. Our results have broad therapeutic implications for the understanding and treatment of neurodegenerative diseases.

中文翻译：

---

响应线粒体损伤，NOT4对ABCE1的泛素化将共翻译质量控制与PINK1定向线粒体联系起来。

mRNA的翻译受到严格的监管，并不断进行错误检查。异常翻译可触发共翻译蛋白和RNA质量控制过程，其损伤会通过尚不清楚的机制导致神经退行性变。在这里，我们显示线粒体外膜（MOM）定位的mRNA的翻译质量控制与受损的线粒体的营业额相交，两者都是由线粒体激酶PINK1精心安排的。线粒体损伤会导致MOM上复合物I 30 kDa亚基（C-I30）mRNA的翻译停滞，从而触发共翻译质量控制因子Pelo，ABCE1和NOT4募集到核糖体/ mRNA-核糖核蛋白复合物中。由NOT4引起的ABCE1损伤诱导的泛素化作用会产生多泛素信号，从而将自噬受体吸引到MOM上以引发线粒体吞噬。在果蝇PINK1模型中，这些因素协同作用以恢复线粒体和神经肌肉组织的完整性。因此，与核糖体相关的共翻译质量控制会产生早期信号来触发线粒体吞噬。我们的结果对神经退行性疾病的理解和治疗具有广泛的治疗意义。