Impaired Peroxisomal Import Triggers a Peroxisomal Retrograde Signaling

Abstract

Distinct retrograde signaling pathways have been identified for several cellular organelles. These pathways are important to maintain the function of these organelles in response to organelle-specific stress. Using\xa0Caenorhabditis elegans, we show for the first time that such a retrograde signaling also exists for peroxisomes. Specifically, peroxisomal import stress caused by the knock-down of the peroxisomal matrix protein import receptor\xa0prx-5/PEX5\xa0triggers the NHR-49/PPARα dependent transcriptional up-regulation of the peroxisomal Lon protease\xa0lonp-2/LONP2\xa0and the peroxisomal catalase\xa0ctl-2/CAT. We also show that impairment of peroxisomal beta-oxidation activates this response. We propose that a reduced import of peroxisomal beta-oxidation enzymes and the resulting change in fatty acid composition is the signal that activates this response. Proteomic analysis revealed that peroxisomal import stress induces the compensatory up-regulation of peroxisomal beta-oxidation enzymes. We, therefore, propose that the peroxisomal retrograde signaling participates in the maintenance of peroxisomal beta-oxidation in response to peroxisomal import stress.