ABSTRACT

INTRODUCTION Peroxisomes are intracytoplasmic, single membrane-bound organelles that play major roles in diverse reactions of lipid metabolism as well as cellular scavenging of peroxides and reactive oxygen species. Many of their functions are highly conserved throughout evolution, although some are unique to particular species.80 Peroxisomes and mitochondria are interrelated biochemically, and defects in both organelles have been reported in the Zellweger spectrum62,158 and adreno-leukodystrophy (ALD). Both peroxisomes and mitochondria are involved in β-oxidation of fatty acids and the α-oxidation of phytanic acid.191 Long-chain fatty acids are predominantly oxidized in mitochondria, whereas oxidation of very long-chain fatty acids (VLCFAs ≥ C22) and branched-chain fatty acids is initiated in peroxisomes and then completed in mitochondria.194 In yeast and plants, fatty acid β-oxidation is confined to peroxisomes. Peroxisomes participate in both generation and scavenging of cellular reactive oxygen species (ROS).162,192 Peroxisomes also have metabolic interactions with endoplasmic reticulum (ER), including breakdown of dicarboxylic acids generated by ω-oxidation of fatty acids in the ER, and activation of hepatic ER stress responses in peroxisomal disorders.80,178 The number, size and function of peroxisomes change dramatically with cellular type and environmental stimuli and common transcriptional regulators, such as peroxisome proliferatoractivated receptors, coordinately control enzyme levels in peroxisomes, mitochondria and ER.80,163 Peroxisomes and mitochondria also share key components of their division machinery and increasing evidence supports a functional interaction of peroxisomes with ER. Peroxisome interactions with lipid droplets and the lysosomal-endosomal system are increasingly recognized. Novel peroxisome functions, such

as signalling platforms for antiviral innate immunity39 and tuberous sclerosis complex regulation of mammalian target of rapamycin (mTORC1) and autophagy in response to ROS,204 continue to be discovered.