Cytosolic PINK1 orchestrates protein translation during proteasomal stress by phosphorylating the translation elongation factor eEF1A1,FEBS Letters

当前位置： X-MOL 学术 › FEBS Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Cytosolic PINK1 orchestrates protein translation during proteasomal stress by phosphorylating the translation elongation factor eEF1A1
FEBS Letters ( IF 3.0 ) Pub Date : 2021-01-06 , DOI: 10.1002/1873-3468.14030
Siyue Qin ₁ , Ling Ye ₂ , Youshi Zheng ₃ , Ju Gao ₃

Affiliation

Mutations in PINK1 (PTEN-induced putative kinase 1) are associated with autosomal recessive early-onset Parkinson's disease. Full-length PINK1 (PINK1-l) has been extensively studied in mitophagy, however, the functions of the short form of PINK1 (PINK1-s) remain poorly understood. Here, we report that PINK1-s is recruited to ribosome fractions after short-term inhibition of proteasomes. Expression of PINK1-s greatly inhibits protein synthesis even without proteasomal stress. Mechanistically, PINK1-s phosphorylates the translation elongation factor eEF1A1 during proteasome inhibition. Expression of the phosphorylation mimic mutation eEF1A1S396E rescues protein synthesis defects and cell viability caused by PINK1 knockout. These findings implicate an important role for PINK1-s in protecting cells against proteasome stress through inhibiting protein synthesis.

中文翻译：

细胞溶质 PINK1 通过磷酸化翻译延伸因子 eEF1A1 来协调蛋白酶体应激期间的蛋白质翻译

PINK1（PTEN 诱导的推定激酶 1）突变与常染色体隐性早发性帕金森病有关。全长 PINK1 (PINK1-l) 已在线粒体自噬中得到广泛研究，然而，PINK1 的短形式 (PINK1-s) 的功能仍然知之甚少。在这里，我们报告在短期抑制蛋白酶体后 PINK1-s 被募集到核糖体部分。即使没有蛋白酶体应激，PINK1-s 的表达也能极大地抑制蛋白质合成。从机制上讲，PINK1-s 在蛋白酶体抑制过程中磷酸化翻译延伸因子 eEF1A1。磷酸化模拟突变 eEF1A1S396E 的表达挽救了由 PINK1 敲除引起的蛋白质合成缺陷和细胞活力。

更新日期：2021-01-06

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11