Chen Min, Zhu Jie-Ying, Mu Wang-Jing, Guo Liang
School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China.
Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai 200438, China.
Genes Dis. 2022 Feb 17;10(3):877-890. doi: 10.1016/j.gendis.2021.12.023. eCollection 2023 May.
Cysteine dioxygenase type 1 (CDO1), belonging to the mammalian non-heme Fe(II) dioxygenases family, is a key enzyme for cysteine catabolism. Its activity and expression is regulated through multiple mechanisms. CDO1 is involved in a spectrum of physiological processes including lipid metabolism, adipogenesis, osteoblastic differentiation, redox homeostasis, fertility, bile acid metabolism, sulfide metabolism, and organismal growth and development. Many of these processes are regulated directly or indirectly by CDO1-mediated metabolism of cysteine. In pathophysiological processes, the degree of promoter methylation is closely related to the progression and malignancy of tumors, and overexpression of CDO1 will promote ferroptosis of cancer cells. Moreover, CDO1 may ameliorate metabolic disorders through the taurine-mediated improvement of lipid metabolism and insulin sensitivity and improve neurodegenerative diseases by regulating cysteine level. Therefore, elucidation of the mechanisms underlying the role of CDO1 would provide a clearer view of the therapeutic potential and possible risks of targeting this important enzyme.
1型半胱氨酸双加氧酶（CDO1）属于哺乳动物非血红素铁（II）双加氧酶家族，是半胱氨酸分解代谢的关键酶。其活性和表达通过多种机制进行调节。CDO1参与一系列生理过程，包括脂质代谢、脂肪生成、成骨细胞分化、氧化还原稳态、生育能力、胆汁酸代谢、硫化物代谢以及机体生长发育。其中许多过程直接或间接受CDO1介导的半胱氨酸代谢调控。在病理生理过程中，启动子甲基化程度与肿瘤的进展和恶性程度密切相关，CDO1的过表达会促进癌细胞的铁死亡。此外，CDO1可能通过牛磺酸介导的脂质代谢改善和胰岛素敏感性提高来改善代谢紊乱，并通过调节半胱氨酸水平改善神经退行性疾病。因此，阐明CDO1作用的潜在机制将更清楚地了解靶向这一重要酶的治疗潜力和可能风险。
