Mechanisms of ferroptosis sensitization and resistance

Abstract

Ferroptosis is an iron-dependent and oxidative form of non-apoptotic cell death with roles in development, homeostasis, and disease. Ferroptosis sensitivity can vary between cells, often for reasons that are not well understood. In this perspective, we describe the core ferroptosis mechanism and outline how changes in iron, redox, and lipid metabolism can alter ferroptosis sensitivity. We propose the concept of a ferroptosis sensitivity-resistance continuum to describe how different intrinsic and extrinsic factors interact to push cells toward a more ferroptosis-sensitive or ferroptosis-resistant state, with effects on development and diseases such as cancer.

Keywords: GPX4; cancer; development; ferroptosis; glutathione; iron; lipid peroxidation; necrosis; neurodegeneration; system xc(−).