Figure 1. The broad range of ROS signalling is influenced by ROS production and catabolism, and by cellular adaptation.

Restriction of reactive oxygen species (ROS) production to appropriate subcellular locations, times, levels, molecular species and for appropriate durations allows ROS to contribute to homeostasis and physiological cell activation. For example, brief pulses of H₂O₂ production at the plasma membrane or at the endosomal membrane mediate signalling in response to the engagement of receptors with cytokines, microbial products or antigens (left-hand side). When ROS production escapes these restrictions — for example, when there are high levels or sustained production of hydroxyl radicals — macromolecules are damaged (‘oxidative stress’). ROS-mediated damage can often be reversed by repair, replacement, degradation or sequestration of the damaged macromolecules (middle). However, damage that exceeds the capacity of the cell for these responses can lead to cell death (right-hand side). When damage to DNA results in mutagenesis without irreparable double-strand breakage, and when damage to other macromolecules is repaired, the consequence can be malignant transformation rather than death of the cell (right-hand side).