# The Ubiquity of the Reaction of the Labile Iron Pool That Attenuates Peroxynitrite-Dependent Oxidation Intracellularly

## TL;DR

The labile iron pool reacts with peroxynitrite to reduce its oxidative effects in cells, potentially influencing iron homeostasis and cell death.

## Contribution

The study demonstrates the antioxidant role of the labile iron pool in peroxynitrite-dependent oxidation across multiple cell types.

## Key findings

- The labile iron pool reacts rapidly with peroxynitrite to attenuate its oxidative impact.
- This reaction may influence iron homeostasis and ferroptosis by altering the redox state of the labile iron pool.
- The reaction appears to be a potential protective mechanism against peroxynitrite in various cell types.

## Abstract

Although the labile iron pool (LIP) biochemical identity remains a topic of debate, it serves as a universal homeostatically regulated and essential cellular iron source. The LIP plays crucial cellular roles, being the source of iron that is loaded into nascent apo-iron proteins, a process akin to protein post-translational modification, and implicated in the programmed cell death mechanism known as ferroptosis. The LIP is also recognized for its reactivity with chelators, nitric oxide, and peroxides. Our recent investigations in a macrophage cell line revealed a reaction of the LIP with the oxidant peroxynitrite. In contrast to the LIP’s pro-oxidant interaction with hydrogen peroxide, this reaction is rapid and attenuates the peroxynitrite oxidative impact. In this study, we demonstrate the existence and antioxidant characteristic of the LIP and peroxynitrite reaction in various cell types. Beyond its potential role as a ubiquitous complementary or substitute protection system against peroxynitrite for cells, the LIP and peroxynitrite reaction may influence cellular iron homeostasis and ferroptosis by changing the LIP redox state and LIP binding properties and reactivity.