Copper-dependent autophagic degradation of GPX4 drives ferroptosis
State Key Laboratory of Respiratory Disease · Guangzhou Medical University · +13 more institutions
Abstract
Ferroptosis is a type of iron-dependent regulated cell death characterized by unrestricted lipid peroxidation and membrane damage. Although GPX4 (glutathione peroxidase 4) plays a master role in blocking ferroptosis by eliminating phospholipid hydroperoxides, the regulation of GPX4 remains poorly understood. Here, we report an unexpected role for copper in promoting ferroptotic cell death, but not cuproptosis, by inducing macroautophagic/autophagic degradation of GPX4. Copper chelators reduce ferroptosis sensitivity but do not inhibit other types of cell death, such as apoptosis, necroptosis, and alkaliptosis. Conversely, exogenous copper increases GPX4 ubiquitination and the formation of GPX4 aggregates by…
Citation impact
- FWCI
- 141.08
- Percentile
- 100%
- References
- 69
Authors
12- QXQian Xue
State Key Laboratory of Respiratory Disease, Guangzhou Medical University
- YDYan Ding
State Key Laboratory of Respiratory Disease, Guangzhou Medical University
- XCXi Chen
State Key Laboratory of Respiratory Disease, Guangzhou Medical University
- XCXi ChenCorresponding
State Key Laboratory of Respiratory Disease, Guangzhou Medical University
- XLXiaofen Li
Southwestern Medical Center, State Key Laboratory of Respiratory Disease, Southwestern Medical Center, The University of Texas Southwestern Medical Center, Guangzhou Medical University
Topics & keywords
- GPX4
- Sequestosome 1
- Autophagy
- Programmed cell death
- Biology
- Phospholipid-hydroperoxide glutathione peroxidase
- Cell biology
- ATG8
- Good health and well-being