Zhu Jinchai, Su Hua
Department of Nephrology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan, Wuhan 430022, China.
iScience. 2025 May 24;28(6):112578. doi: 10.1016/j.isci.2025.112578. eCollection 2025 Jun 20.
Stress granules (SGs), transient membraneless biomolecular condensates assembling dynamically under stress conditions, mainly comprise untranslated mRNAs and RNA-binding proteins (RBPs) to orchestrate cellular stress adaptation. SGs biogenesis progresses through translation arrest-induced mRNA condensation, liquid-liquid phase separation (LLPS)-mediated assembly, and subsequent maturation, while their disassembly enables translational recovery after stress relief. SGs emerge as promising therapeutic targets through dynamic regulation to counteract stress conditions, yet their pathological dysregulation disrupts cellular homeostasis, positioning these dynamic biomolecular as potential therapeutic targets through modulation of their assembly and disassembly equilibrium. While SGs biogenesis-disassembly mechanisms in renal contexts remain enigmatic, this review systematically examines their interplay with pathological state (e.g., hyperosmolarity, acidosis, and aging) and dual roles in renal pathophysiology - facilitating repair or driving progression in acute kidney injury, kidney cancer, and hereditary nephropathies. Our synthesis of SGs mediated stress adaptation mechanisms highlights critical knowledge gaps in nephrology.
应激颗粒(SGs)是在应激条件下动态组装的瞬时无膜生物分子凝聚物,主要由未翻译的mRNA和RNA结合蛋白(RBPs)组成,以协调细胞应激适应。SGs的生物发生通过翻译停滞诱导的mRNA凝聚、液-液相分离(LLPS)介导的组装以及随后的成熟过程进行,而它们的解体则使应激缓解后能够恢复翻译。通过动态调节以应对应激条件,SGs成为有前景的治疗靶点,然而它们的病理失调会破坏细胞稳态,通过调节其组装和解离平衡将这些动态生物分子定位为潜在的治疗靶点。虽然肾脏环境中SGs的生物发生-解体机制仍然不明,但本综述系统地研究了它们与病理状态(如高渗、酸中毒和衰老)的相互作用以及在肾脏病理生理学中的双重作用——在急性肾损伤、肾癌和遗传性肾病中促进修复或推动疾病进展。我们对SGs介导的应激适应机制的综合分析突出了肾脏病学中的关键知识空白。