Chen Fangquan, Kang Rui, Liu Jiao, Tang Daolin
DAMP Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 511436, China.
Biology (Basel). 2023 Jun 15;12(6):864. doi: 10.3390/biology12060864.
Lipid metabolism, cell death, and autophagy are interconnected processes in cells. Dysregulation of lipid metabolism can lead to cell death, such as via ferroptosis and apoptosis, while lipids also play a crucial role in the regulation of autophagosome formation. An increased autophagic response not only promotes cell survival but also causes cell death depending on the context, especially when selectively degrading antioxidant proteins or organelles that promote ferroptosis. ACSL4 is an enzyme that catalyzes the formation of long-chain acyl-CoA molecules, which are important intermediates in the biosynthesis of various types of lipids. ACSL4 is found in many tissues and is particularly abundant in the brain, liver, and adipose tissue. Dysregulation of ACSL4 is linked to a variety of diseases, including cancer, neurodegenerative disorders, cardiovascular disease, acute kidney injury, and metabolic disorders (such as obesity and non-alcoholic fatty liver disease). In this review, we introduce the structure, function, and regulation of ACSL4; discuss its role in apoptosis, ferroptosis, and autophagy; summarize its pathological function; and explore the potential implications of targeting ACSL4 in the treatment of various diseases.
脂质代谢、细胞死亡和自噬是细胞中相互关联的过程。脂质代谢失调可导致细胞死亡，例如通过铁死亡和凋亡，而脂质在自噬体形成的调节中也起着关键作用。自噬反应增强不仅能促进细胞存活，还会根据具体情况导致细胞死亡，特别是当选择性降解促进铁死亡的抗氧化蛋白或细胞器时。ACSL4是一种催化长链酰基辅酶A分子形成的酶，长链酰基辅酶A分子是各种脂质生物合成中的重要中间体。ACSL4存在于许多组织中，在大脑、肝脏和脂肪组织中尤为丰富。ACSL4失调与多种疾病有关，包括癌症、神经退行性疾病、心血管疾病、急性肾损伤和代谢紊乱（如肥胖和非酒精性脂肪性肝病）。在本综述中，我们介绍了ACSL4的结构、功能和调节；讨论了其在凋亡、铁死亡和自噬中的作用；总结了其病理功能；并探讨了靶向ACSL4在各种疾病治疗中的潜在意义。
