Raising the iron curtain: Lactate's secret role in oxidative stress defense

The hypothesis presented here is that certain cell types under oxidative stress, such as cancer cells, reprogram their metabolism to accumulate lactate, along with cytosolic Fe²⁺ within the labile iron pool, thereby establishing a metabolite-based H₂O₂ detoxification system. In this scenario, the Fenton reaction between Fe²⁺ and H₂O₂ generates hydroxyl radicals (HO•), which are subsequently scavenged by abundant lactate. Thus, lactate production may function as a protective, iron-dependent antioxidant mechanism, enabling cells to decompose H₂O₂ and prevent damage to crucial biomolecules. If this system is compromised, for instance by inadequate HO•-scavenging or impaired Fe²⁺ recycling, cells may become prone to ferroptosis.