Peroxisomes are ubiquitous organelles that contain catalase and oxidative enzymes producing H₂O₂. Depending on cell type, their number, shape, and size vary. By electron microscopy, peroxisomes have a single membrane that encloses a dense matrix that contains a crystalloid core in some species (e.g., rat hepatocytes) but not in others (e.g., human hepatocytes). The typical fine structure of peroxisomes (PO) in rat liver hepatocytes with a dense crystalloid core (asterisk) is shown in panel A, which also illustrates how they differ in their fine structure from mitochondria (M). Cisternae of the endoplasmic reticulum (ER) can be closely associated with peroxisomes and with mitochondria (cf. Fig. 97). Usually, peroxisomes are spherical, with a diameter as large as 1 μm in hepatocytes and as small as 0.1 μm in fibroblasts. However, in kidney tubular cells they may be angular. In specialized mammalian cells, proliferating hepatocytes after partial hepatectomy and some yeast, peroxisomes may form an interconnected network of tubules and cup-shaped structures, which are referred to as peroxisomal networks.

A main function of peroxisomes is lipid metabolism. Oxidases catabolize long-chain unsaturated fatty acids by β-oxidation to acetyl CoA, and β-oxidize bile acid intermediates, leukotrienes, and prostaglandins. The oxidative enzymes use molecular oxygen to carry out oxidative reactions that result in the formation of hydrogen peroxide. Hydrogen peroxide is used by peroxisomal catalase to oxidize substrates such as alcohol, phenol, formaldehyde, and formic acid. In hepatocyte and kidney epithelia, this represents an important detoxification reaction. In the liver, peroxisomes function in cholesterol metabolism and gluconeogenesis. In the central nervous system, peroxisomes catalyze the first biosynthetic reaction in the formation of plasmalogens, the most abundant class of myelin phospholipids. In the sebaceous glands of skin, they are involved in the synthesis of complex lipids in sebum.

Immunoelectron microscopy has shown a remarkable degree of compartmentation in peroxisomes. Catalase was detectable in the matrix but not in the crystalloid core of rat hepatocyte peroxisomes (panel B). On the contrary, urate oxidase (panel C), α-hydroxy acid oxidase A, and xanthine oxidase were confined to the crystalloid core. These cores are composed of parallel bundles of hollow tubules. Ten primary tubules (5 nm inner diameter) are arranged in a circle and form a centrally located secondary tubule (20 nm outer diameter). Remarkably, both urate and xanthine oxidase were restricted to the lumen of primary tubules. An extreme example of compartmentation was observed for angular peroxisomes of beef kidney. The crystalline core contained urate oxidase, the noncrystalline central region of the matrix D-amino acid oxidase, the peripheral matrix region catalase and α-hydroxy acid oxidase A, and the marginal dense plates close but separated from the peroxisomal membrane α-hydroxy acid oxidase B. Panel D shows the presence of the 70 kDa peroxisomal membrane protein (PMP-70). Under conditions of peroxisome proliferation, the PMP-70 was found not only along the peroxisomal membrane (panel D) but additionally in membranous loops in continuity with it.

Originally, the endoplasmic reticulum was proposed as the source of peroxisomes. More recently, this concept has been revived. There is ample evidence that most peroxisomal membrane proteins after synthesis on polysomes enter the rough endoplasmic reticulum via the Sec61 translocon and a few through the GET (Golgi to ER Traffic) complex. The peroxisomal membrane proteins Pex3, Pex13, and PMP-70 assemble in endoplasmic reticulum subdomains and give rise to preperoxisomal vesicles through budding. Pex19 and Pex16, which are mostly cytosolic proteins, become enriched at the Pex3 endoplasmic reticulum subdomains and are required for the budding process. This is followed by heterotypic fusion of preperoxisomes to form import-competent preperoxisomes. Then import of peroxisomal matrix proteins results in the formation of mature peroxisomes. In contrast to the membrane proteins, peroxisomal matrix proteins are directly imported from the cytosol into the (pre-)peroxisomes. Their targeting depends on two different peroxisomal targeting signals. The translocation of peroxisomal matrix proteins is a multistep process involving the importomer of the peroxisomal membrane.