Figure 4. The different roles of mitochondrial CLPXP.

The proteolytic component CLPP degrades misfolded mitochondrial proteins in C. elegans to initiate UPR^mt stress signalling, which leads to the induction of nuclear-encoded mitochondrial protective genes¹⁵. Our study identifies specific proteins and pathways that are likely targets of CLPXP, suggesting a dedicated role of this protease in regulation and maintenance of mitochondrial energy metabolism. The observation that CLPP-knockdown in cancer cells impairs oxidative phosphorylation is in support of this emerging view¹⁷. Furthermore, several chaperones and components of other mitochondrial pathways, e.g. those controlling translation, redox homeostasis, and amino acid biosynthesis, were found as additional potential targets or interactors of CLPXP.