Unfolded protein responses in bacteria and mitochondria: a central role for the ClpXP machine

Abstract

In the crowded environment of a cell, the protein quality control machinery, such as molecular chaperones and proteases, maintains a population of folded and hence functional proteins. The accumulation of unfolded proteins in a cell is particularly harmful as it not only reduces the concentration of active proteins but also overburdens the protein quality control machinery, which in turn, can lead to a significant increase in nonproductive folding and protein aggregation. To circumvent this problem, cells use heat shock and unfolded protein stress response pathways, which essentially sense the change to protein homeostasis upregulating protein quality control factors that act to restore the balance. Interestingly, several stress response pathways are proteolytically controlled. In this review, we provide a brief summary of targeted protein degradation by AAA+ proteases and focus on the role of ClpXP proteases, particularly in the signaling pathway of the Escherichia coli extracellular stress response and the mitochondrial unfolded protein response.