Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Biomolecules. 2024 Oct 28;14(11):1369. doi: 10.3390/biom14111369.
Endoplasmic reticulum (ER) stress is a cellular phenomenon that arises in response to the accumulation of misfolded proteins within the ER. This process triggers the activation of a signalling pathway known as the unfolded protein response (UPR), which aims to restore ER homeostasis by reducing protein synthesis, increasing protein degradation, and promoting proper protein folding. However, excessive ER stress can perturb regular cellular function and contribute to the development of diverse pathological conditions. As is well known, ferroptosis is a kind of programmed cell death characterized by the accumulation of lipid peroxides and iron-dependent reactive oxygen species (ROS), resulting in oxidative harm to cellular structures. In recent years, there has been increasing evidence indicating that ferroptosis occurs in musculoskeletal disorders (MSDs), with emerging recognition of the complex relationship between ER stress and ferroptosis. This review presents a summary of ER stress and the ferroptosis pathway. Most importantly, it delves into the significance of ER stress in the ferroptosis process within diverse skeletal or muscle cell types. Furthermore, we highlight the potential benefits of targeting the correlation between ER stress and ferroptosis in treating degenerative MSDs.
内质网（ER）应激是一种细胞现象，是由于 ER 内错误折叠的蛋白质积累而引起的。这一过程触发了一种被称为未折叠蛋白反应（UPR）的信号通路的激活，其目的是通过减少蛋白质合成、增加蛋白质降解和促进适当的蛋白质折叠来恢复 ER 稳态。然而，过度的 ER 应激会扰乱正常的细胞功能，并导致多种病理状况的发展。众所周知，铁死亡是一种程序性细胞死亡，其特征是脂质过氧化物和铁依赖性活性氧（ROS）的积累，导致细胞结构的氧化损伤。近年来，越来越多的证据表明铁死亡发生在肌肉骨骼疾病（MSD）中，人们对 ER 应激和铁死亡之间的复杂关系有了新的认识。这篇综述总结了 ER 应激和铁死亡途径。最重要的是，它深入探讨了 ER 应激在不同的骨骼或肌肉细胞类型中铁死亡过程中的意义。此外，我们强调了靶向 ER 应激和铁死亡相关性在治疗退行性 MSD 中的潜在益处。
