Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Hear Res. 2023 Sep 1;436:108821. doi: 10.1016/j.heares.2023.108821. Epub 2023 Jun 1.
Orchestration of protein production and degradation and the regulation of protein lifetimes play a central role in many basic biological processes. Nearly all mammalian proteins are replenished by protein turnover in waves of synthesis and degradation. Protein lifetimes in vivo are typically measured in days, but a small number of extremely long-lived proteins (ELLPs) persist for months or even years. ELLPs are rare in all tissues but are enriched in tissues containing terminally differentiated post-mitotic cells and extracellular matrix. Consistently, emerging evidence suggests that the cochlea may be particularly enriched in ELLPs. Damage to ELLPs in specialized cell types, such as crystallin in the lens cells of the eye, causes organ failure such as cataracts. Similarly, damage to cochlear ELLPs is likely to occur with many insults, including acoustic overstimulation, drugs, anoxia, and antibiotics, and may play an underappreciated role in hearing loss. Furthermore, hampered protein degradation may contribute to acquired hearing loss. In this review, I highlight our knowledge of the lifetimes of cochlear proteins with an emphasis on ELLPs and the potential contribution that impaired cochlear protein degradation has on acquired hearing loss and the emerging relevance of ELLPs.
蛋白质的合成和降解的协调以及蛋白质寿命的调控在许多基本的生物学过程中起着核心作用。几乎所有的哺乳动物蛋白质都是通过一波又一波的合成和降解来补充的。体内蛋白质的寿命通常以天来衡量，但一小部分极长寿命的蛋白质（ELLP）可以持续数月甚至数年。在所有组织中，ELLP 都很少见，但在含有终末分化的有丝分裂后细胞和细胞外基质的组织中富集。一致地，新出现的证据表明，耳蜗可能特别富含 ELLP。在特定的细胞类型中，如眼晶状体细胞中的晶体蛋白，ELLP 的损伤会导致器官衰竭，如白内障。同样，耳蜗 ELLP 的损伤可能会发生在许多情况下，包括声过度刺激、药物、缺氧和抗生素，并且可能在听力损失中起着被低估的作用。此外，蛋白质降解受阻可能导致获得性听力损失。在这篇综述中，我强调了我们对耳蜗蛋白质寿命的认识，重点是 ELLP，以及受损的耳蜗蛋白质降解对获得性听力损失的潜在贡献，以及 ELLP 的新兴相关性。
