Biogenesis, the function of peroxisomes, and their role in genetic disease: With a focus on the ABC transporter

Abstract

Peroxisomes are organelles that are present in almost all eukaryotic cells. These organelles were first described in 1954, in the cytoplasm of the proximal tubule cells in the mouse kidney, using electron microscopy by Rhodin and referred to as “microbodies”. Then, de Duve and Baudhuin isolated microbodies from rat liver using density gradient centrifugation, defined the microbodies as membrane-bound organelles containing several H 2 O 2 -producing oxidases and H 2 O 2 -degrading catalase, and named them peroxisomes. At present, the biogenesis of peroxisomes in mammals involves three different processes: the formation of pre-peroxisomes from the endoplasmic reticulum, the import of peroxisomal membrane and matrix proteins to the pre-peroxisomes, and the growth and division of the peroxisomes. These organelles are involved in a variety of metabolic processes, including the β-oxidation of very long chain fatty acids, and the synthesis of ether phospholipids and bile acids in mammals. These metabolic pathways require the transport of metabolites in and out of peroxisomes. The transport of such metabolites is facilitated in part by the ATP-binding cassette (ABC) transporter. Impairment of the biogenesis and function of peroxisomes causes severe peroxisomal disorders. Since I began peroxisome research at Professor de Duve’s laboratory in 1985, I have studied the biogenesis and function of peroxisomes and peroxisome diseases for more than 30 years, with a focus on ABC transporters. Here, I review the biogenesis of peroxisomes, the targeting of ABC transporters to the peroxisome, and the function of ABC transporters in physiological and pathological processes, including X-linked adrenoleukodystrophy, a neurodegenerative disease.