Ferroptosis is regulated cell death due to failed quality control?
Group of answer choices
True
False
The correct answer and explanation is:
The correct answer is True.
Ferroptosis is a form of regulated cell death that is distinct from other types of cell death like apoptosis and necrosis. It is characterized by the accumulation of lipid peroxides to lethal levels, which leads to cellular damage. This type of cell death is triggered when cells are unable to maintain proper quality control over their lipid metabolism, specifically the oxidation of polyunsaturated fatty acids in their cell membranes.
The central mechanism of ferroptosis involves iron-dependent lipid peroxidation. The accumulation of reactive oxygen species (ROS) causes oxidative damage to cell membranes, particularly to polyunsaturated fatty acids. These damaged lipids, if not properly repaired, will lead to membrane rupture and the eventual death of the cell. A crucial component in this process is the enzyme glutathione peroxidase 4 (GPX4), which normally acts to reduce lipid peroxides. When this enzyme is inhibited or defective, ferroptosis is more likely to occur.
Ferroptosis is considered a failed quality control process because it results from the inability of the cell to manage oxidative stress and lipid oxidation. Normally, cells have mechanisms in place to repair or remove damaged lipids, but when these mechanisms fail, it can trigger ferroptosis. Additionally, cellular iron levels must be tightly regulated because excess iron can promote the production of ROS, further increasing the chances of ferroptosis. Therefore, ferroptosis reflects a breakdown in the cell’s ability to control its internal environment, particularly in relation to iron metabolism and oxidative stress.
This type of regulated cell death has been linked to various pathological conditions, including neurodegenerative diseases, cancer, and ischemia-reperfusion injury. Understanding ferroptosis and its regulation is critical for developing new therapeutic approaches to these diseases.