What is the major function of peroxisomes?
Peroxisomes are ubiquitous single-membrane organelles present in most eukaryotes central to lipid metabolism, ROS balance, and signaling. Their hallmark metabolic function is beta-oxidation of very-long-chain fatty acids longer than 22 carbons, branched-chain fatty acids like phytanic acid requiring alpha-oxidation first, and polyunsaturated fatty acids that mitochondria cannot handle efficiently due to double bond positions. Unlike mitochondrial beta-oxidation coupled to electron transfer flavoprotein and respiratory chain to produce ATP, peroxisomal acyl-CoA oxidases, ACOX1, ACOX2, ACOX3, transfer electrons directly to molecular oxygen, generating hydrogen peroxide as byproduct. Enzymes include acyl-CoA oxidase, bifunctional protein with hydratase and dehydrogenase activities, and 3-ketoacyl-CoA thiolase. Acetyl-CoA and chain-shortened acyl-CoAs are then exported to mitochondria either as free acetate or via carnitine shuttle for complete oxidation to CO2. Peroxisomes also initiate ether phospholipid plasmalogen synthesis necessary for myelin, bile acid side chain oxidation, glyoxylate detoxification, and polyamine catabolism. Import of matrix proteins uses cytosolic receptors PEX5 recognizing C-terminal PTS1 SKL tripeptide and PEX7 recognizing N-terminal PTS2. Defective import causes Zellweger spectrum disorders with severe neurodevelopmental defects.
Ref: Wanders & Waterham, Annual Review of Biochemistry 2016: Peroxisome Biogenesis and Fatty Acid Beta-Oxidation.