Ferroptosis: Iron-Induced Cell Death

The Signature of Tissue Death in Iron Overloaded Bodies

The body of research on iron overload and it’s link to obesity and chronic illnesses is massive. Most of what I’ve read implicates a combination of overwhelmed antioxidant systems leading to inflammation and a process called Ferroptosis, which is iron induced cell death.

Ferroptosis, the cellular process underlying the damage that iron overload causes in the body, was first described by Scott Dixon in 2012 in this Cell paper:

Ferroptotic death is morphologically, biochemically, and genetically distinct from apoptosis, various forms of necrosis, and autophagy. This process is characterized by the overwhelming, iron-dependent accumulation of lethal lipid ROS (Reactive Oxygen Species).

A 2023 review on the role of ferroptosis in obesity outlines key points on ferroptosis uncovered since Dixon’s discovery in 2012:

• Ferroptosis is an iron-dependent regulated cell death (RCD) caused by iron overload and reactive oxygen species (ROS)-dependent excessive accumulation of lipid peroxidation.

• Ferroptosis is characterized by changes in mitochondrial morphology, including mitochondrial shrinkage, reduced or absent mitochondrial cristae, and increased mitochondrial membrane density.

• It’s bioenergetic features are iron accumulation and lipid peroxidation.

• It has been established that ferroptosis is involved in the initiation and progression of many diseases.

This figure from that paper outlines diseases linked to ferroptosis:

Mechanistic studies on ferroptosis show that iron induced cell death can be inhibited by iron chelators, which soak up excess iron. This implies that the solution might be very simple.

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