Raising the iron curtain: Lactate's secret role in oxidative stress defense
Astrid Hensel, Renáta Váraljai, Shirley K. Knauer
Abstract
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 Fe 2+ within the labile iron pool, thereby establishing a metabolite-based H 2 O 2 detoxification system. In this scenario, the Fenton reaction between Fe 2+ and H 2 O 2 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 H 2 O 2 and prevent damage to crucial biomolecules. If this system is compromised, for instance by inadequate HO•-scavenging or impaired Fe 2+ recycling, cells may become prone to ferroptosis.