Understanding the Activity of Insulin Degrading Enzyme at the Peroxisome

Insulin Degrading Enzyme (IDE) is a metalloprotease implicated in the degradation of peptides relevant to type II diabetes and Alzheimer’s. IDE has been shown to localize to the peroxisome but its activity there is unknown. We assert that the cleaved type-II peroxisome signaling peptide (PTSIIp) of peroxisomal thiolase is a substrate of IDE and may play a regulatory role in peroxisome import. We also investigate activity of IDE against Pex5, a cytosolic receptor crucial to import. We test this using a Forster Resonance Energy Transfer (FRET)-based competition assay of IDE and relevant IDE mutants paired with cycloheximide (CHX) chase experiments in human cell models. By understanding how IDE affects peroxisome import, we can ultimately understand the impact of peroxisomes on relevant human diseases.