Investigating the import of folded proteins into peroxisomes

Abstract

Peroxisomes are essential organelles that play a critical role in a variety of metabolic pathways, such as the oxidation of fatty acids and the biosynthesis of certain amino acids and steroids. In addition, these organelles segregate toxic reactive oxygen species, including hydrogen peroxide and superoxide anions, from the rest of the cell to prevent damage to proteins and nucleic acids associated with many diseases. To support these functions, the peroxisome must recognize and transport over 100 distinct proteins from the cytoplasm into the peroxisomal matrix. Recent studies have established that in contrast to several other cellular organelles, which import proteins as unfolded polypeptides, peroxisomes are capable of transporting folded and even oligomeric proteins across its membrane. Although nearly twenty proteins have been implicated in this translocation process, the mechanistic details of import are still unclear. Herein, we present our work which addresses the initial docking stage of peroxisomal protein import using a combination of biochemical and biophysical methods, and outline ongoing studies to address the precise mechanism by which folded proteins are translocated across the peroxisomal membrane.