Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, Department of Medicine, Division of Hematology/Oncology, New York, 10029, NY, USA.
Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, Department of Medicine, Division of Hematology/Oncology, New York, 10029, NY, USA.
Mol Cell Neurosci. 2019 Jul;98:12-18. doi: 10.1016/j.mcn.2019.04.003. Epub 2019 Apr 24.
The mitochondrial unfolded protein response (UPR) is rapidly gaining attention. While the CHOP (ATF4/5) axis of the UPR was the first to be described, other axes have subsequently been reported. Validation of this complex pathway in C. elegans has been extensively studied. However, validation of the UPR in mouse models of disease known to implicate mitochondrial reprogramming or dysfunction, such as cancer and neurodegeneration, respectively, is only beginning to emerge. This review summarizes recent findings and highlights the major role of the superoxide dismutase SOD1 in the communication between the mitochondria and the nucleus in these settings. While SOD1 has mostly been studied in the context of familial amyotrophic lateral sclerosis (fALS), recent studies suggest that SOD1 may be a potentially important mediator of the UPR and converge to emphasize an increasingly vital role of SOD1 as a therapeutic target in cancer.
线粒体未折叠蛋白反应 (UPR) 正受到越来越多的关注。虽然 UPR 的 CHOP（ATF4/5）轴是最早被描述的，但随后也报道了其他轴。该复杂途径在秀丽隐杆线虫中的验证已得到广泛研究。然而，在已知涉及线粒体重编程或功能障碍的疾病的小鼠模型中验证 UPR，例如癌症和神经退行性变，才刚刚开始出现。本综述总结了最近的发现，并强调了超氧化物歧化酶 SOD1 在这些情况下线粒体和核之间通讯中的主要作用。虽然 SOD1 主要在家族性肌萎缩侧索硬化症 (fALS) 的背景下进行了研究，但最近的研究表明，SOD1 可能是 UPR 的一个潜在重要介质，并强调 SOD1 作为癌症治疗靶点的作用日益重要。
