Evolution of the cellular stress proteome: from monophyletic origin to ubiquitous function

Cells respond to acute environmental change by activating a stress response that is widely studied. However, knowledge of this stress response is fragmentary, and a unifying concept explaining its universality for many different species and types of stress is lacking. The need for a holistic view emphasizing the key aspects of the stress response is addressed by the following hypothesis. The cellular stress response is a reaction to any form of macromolecular damage that exceeds a set threshold, independent of the underlying cause. It is aimed at temporarily increasing tolerance limits towards macromolecular damage by utilizing a phylogenetically conserved set of genes and pathways that mediate global macromolecular stabilization and repair to promote cellular and organismal integrity under suboptimal conditions. This mechanism affords time for a separate set of stressor-specific adaptations, designed to re-establish cellular homeostasis, to take action. Supporting evidence, emerging conclusions, and ways to test this hypothesis are presented.