Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. However, the physiological role of SGs in organismal aging and longevity regulation remains unclear. In this study, we used TIAR-1::GFP and GTBP-1::GFP as markers to monitor the formation of SGs in Caenorhabditis elegans. We found that, in addition to acute heat stress, SG formation could also be triggered by dietary changes, such as starvation and dietary restriction (DR). We found that HSF-1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK-eEF2K signaling is required for starvation and DR-induced SG formation but not heat shock. Moreover, our data suggest that this AMPK-eEF2K pathway-mediated SG formation is required for lifespan extension by DR, but dispensable for the longevity by reduced insulin/IGF-1 signaling. Collectively, our findings unveil a novel role of SG formation in DR-induced longevity.

译文

应力颗粒 (SGs) 是非膜细胞器,可响应各种压力源而动态组装和拆卸。在压力条件下,多腺苷酸化mrna和翻译因子被隔离在SGs中,以促进蛋白质合成的整体抑制。先前已证明SG的形成可增强细胞存活和抗逆性。然而,SGs在机体衰老和寿命调节中的生理作用仍不清楚。在这项研究中,我们使用TIAR-1::GFP和GTBP-1::GFP作为标记来监测秀丽隐杆线虫中SGs的形成。我们发现,除了急性热应激外,饮食变化 (例如饥饿和饮食限制 (DR)) 也可能触发SG的形成。我们发现,响应急性热休克和饥饿的SG形成需要HSF-1,而不是DR,而饥饿和DR诱导的SG形成需要AMPK-eEF2K信号传导,而不是热休克。此外,我们的数据表明,这种AMPK-eEF2K途径介导的SG形成是DR延长寿命所必需的,但由于胰岛素/IGF-1信号传导减少而延长寿命是必不可少的。总的来说,我们的发现揭示了SG形成在DR诱导的寿命中的新作用。

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