Peroxisomes in human health and disease: metabolic pathways, metabolite transport, interplay with other organelles and signal transduction

Abstract

Peroxisomes play a key role in human physiology as exemplified by the devastating consequences of a defect in peroxisome biogenesis as observed in patients affected by Zellweger syndrome. The main metabolic functions of peroxisomes in humans include: (1) fatty acid beta-oxidation; (2) etherphospholipid synthesis; (3) bile acid synthesis; (4) fatty acid alpha-oxidation, and (5) glyoxylate detoxification. Since peroxisomes lack a citric acid cycle and respiratory chain like mitochondria do, metabolism in peroxisomes requires continued cross-talk with other organelles, notably mitochondria and the endoplasmic reticulum in order to allow continued metabolism of the products generated by peroxisomes. Many of the metabolites which require peroxisomes for homeostasis, are involved in signal transduction pathways. These include the primary bile acids; platelet activating factor; plasmalogens, N-acylglycines and N-acyltaurines; docosahexaenoic acid as well as multiple prostanoids. The current state of knowledge in this area will be discussed in this review.