Insulin-degrading enzyme exists inside of rat liver peroxisomes and degrades oxidized proteins

Insulin-degrading enzyme (IDE) was detected by immunoblot analysis in highl y purified rat liver peroxisomes. IDE in the peroxisomal fraction was resis tant to proteolysis by trypsin and chymotrypsin under conditions where the peroxisomal membranes remained intact. After sonication of the peroxisomal fraction, IDE was recovered in the supernatant fraction. Further, the local ization of IDE in the peroxisomes was shown by immunoelectron microscopy. I n addition, IDE isolated from peroxisomes degraded insulin as well as oxidi zed lysozyme as a model substrate for oxidized proteins. These results sugg est that IDE exists in an active form in the matrix of rat liver peroxisome s and is involved in elimination of oxidized proteins in peroxisomes.