Molecular Biology of the Cell - Volume 2 - Alberts B., Bray D., Lewis J., Raff M., Roberts K., Watson J. 1993

Intracellular Macromolecular Sorting and the Maintenance of Cellular Compartments
Peroxisomes

Peroxisomes (also referred to as Microbodies) differ significantly from Cell/35.html">Mitochondria and METABOLISM/14.html">Chloroplasts. First and foremost, they are bounded by a single membrane and lack both DNA and Ribosomes. Because peroxisomes do not possess their own genome, all of their Proteins must be imported from the Cytosol. In this respect, peroxisomes resemble the ER: they function as self-replicating membranous Organelles that exist without their own genome.

Before examining peroxisome biogenesis, we will focus on the Functions of this diverse family of organelles. Although peroxisomes are found in all Eukaryotic Cells, their functions vary widely across different cell types.

In the early 1960s, it was demonstrated that the major source of at least three oxidative Enzymes—D-Amino Acid Oxidase, urate oxidase, and catalase—consists of distinct organelles with a diameter of about 0.5 µm. In mammals, peroxisomes of this size are found predominantly in the Liver. In electron micrographs, they can be distinguished by a "crystalline" core composed of urate oxidase (Fig. 8-32). Later, once histochemical staining for catalase—an enzyme accounting for up to 40% of total peroxisomal protein—was developed, it was shown that peroxisomes are present in all cells. In most cells, peroxisomes are smaller (0.15–0.25 µm in diameter) than those in liver cells.

Like mitochondria, the peroxisome is one of the primary centers of oxygen utilization in The Cell. According to one hypothesis, the peroxisome represents a remnant of an ancient organelle that performed all oxygen metabolism functions in the primitive ancestors of eukaryotic cells. When oxygen produced by photosynthetic Bacteria began to accumulate in the atmosphere, it was likely toxic to most cells. Peroxisomes may have served to lower intracellular oxygen concentrations while simultaneously harnessing its chemical reactivity to drive essential oxidative reactions. From this perspective, the subsequent emergence of mitochondria rendered peroxisomes largely superfluous, as many reactions that previously occurred in peroxisomes without energy production were now coupled to the generation of ATP via Oxidative Phosphorylation. Thus, the oxidative reactions operating in modern cells are possibly those that remained necessary despite the advent of mitochondria.

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Fig. 8-32. Electron micrograph of three peroxisomes in a rat liver cell. The paracrystalline electron-dense inclusions consist of the enzyme urate oxidase. (Courtesy of Daniel S. Friend.)

8.5.1. Peroxisomes Use Molecular Oxygen and Hydrogen Peroxide in Oxidation Reactions [29]

Peroxisomes derived their name from the fact that they typically contain one or more enzymes that use molecular oxygen to remove hydrogen atoms from specific organic substrates (denoted here as R) in an oxidative reaction that produces hydrogen peroxide (H₂O₂):

RH₂ + О₂→ R + Н₂О₂

Catalase uses the H₂O₂ generated by Other Enzymes in the peroxisome to oxidize a variety of substrates—such as phenols, formic acid, formaldehyde, and alcohol—via a "peroxidative" reaction: H₂O₂ + R'H₂→ R' + 2Н₂О. This type of oxidative reaction is especially important in liver and Kidney cells, whose peroxisomes detoxify numerous harmful substances entering the bloodstream. Nearly half of the ethanol we ingest is oxidized to acetaldehyde in this manner. Furthermore, when excess H₂O₂ accumulates in the cell, catalase converts it to H₂O (2Н₂О₂→ 2Н₂О + О₂).

Fig. 8-33. Cytology/cytology/93.html">ELECTRON MICROGRAPHS OF Two Types of peroxisomes found in plant cells. A. A peroxisome with a paracrystalline core in a tobacco leaf mesophyll cell. Its close association with chloroplasts is thought to facilitate the exchange of Materials between these organelles during Photorespiration. B. Peroxisomes in a lipid-storing cotyledon cell of a tomato seed, 4 days after germination. Here, the peroxisomes (glyoxysomes) are associated with lipid bodies that store fat, reflecting their central role in fat mobilization and Gluconeogenesis during seed germination. (A—courtesy of P. Gruber and E. Newcomb; B—courtesy of S. Frederick and E. Newcomb.)

Peroxisomes are remarkably diverse organelles, containing vastly different sets of enzymes in different cells of even the same Organism. In some cases, the size of peroxisomes changes depending on environmental conditions. For example, Yeast cells growing on a sugar-containing medium have small peroxisomes. However, if these cells are cultured on a methanol-containing medium, large methanol-oxidizing peroxisomes appear; if Fatty acids are present in the medium, large peroxisomes develop in which fatty acids are degraded to acetyl-CoA.

Peroxisomes play a particularly crucial role in plant cells. Two very distinct types of peroxisomes are well-characterized in plants. One type is found in leaves (Fig. 8-33A). These peroxisomes catalyze The oxidation of a byproduct generated when CO₂ is converted into CARBOHYDRATES (an oxidative process known as photorespiration because it consumes O₂ and releases CO₂). Another type of peroxisome is found in germinating seeds (Fig. 8-33B). Here, they function to convert fatty acids stored in plant Lipids into the sugars required for the growth of the young seedling. Because this conversion of fats to sugars proceeds through a series of reactions known as The Glyoxylate cycle, such peroxisomes are also referred to as

glyoxysomes. In the glyoxylate cycle, two molecules of acetyl-CoA produced by fatty acid breakdown within the peroxisome are used to synthesize succinate, which then exits the peroxisome and is converted into glucose. Animal cells lack the glyoxylate cycle and are therefore incapable of converting fatty acids stored in fats into carbohydrates.

Fig. 8-34. A model for peroxisome assembly. The peroxisomal membrane contains specific receptor proteins for import. All peroxisomal proteins, including new copies of these receptors, are synthesized by cytosolic ribosomes and subsequently imported from the cytosol into the peroxisome. Consequently, peroxisomes arise exclusively from pre-existing peroxisomes via growth and division; much like mitochondria and chloroplasts, they continuously import new components from the cytosol.

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8.5.2. All Peroxisomal Components Derive from the Cytosol [30]

Peroxisomes can be viewed as a population of organelles that share a common membrane but contain diverse contents. As noted previously, they lack DNA and ribosomes; all of their proteins are encoded by nuclear genes and synthesized in the cytosol. Both Membrane Proteins and matrix proteins of peroxisomes are imported post-translationally from the cytosol. Among all peroxisomal proteins, catalase has been studied in the most detail. It is a homotetrameric hemoprotein synthesized in the cytosol as heme-free monomers. The monomers are imported into the peroxisomal lumen, where they assemble into tetramers in the presence of heme. Although catalase lacks a cleavable N-terminal signal sequence, it must possess a targeting signal that directs it to the peroxisome. According to recent findings, this role is played, at least in part, by a specific tripeptide sequence located near the carboxy-terminus of many peroxisomal proteins.

Peroxisomes appear to contain at least one unique protein on their cytosolic membrane surface that functions as a receptor, recognizing the targeting signal on an incoming protein. At one time, it was believed that the peroxisomal membrane "shell" formed by budding from the ER, whereas its contents were imported from the cytosol. Currently, a substantial body of evidence demonstrates that new peroxisomes always arise from pre-existing ones through organelle growth and fission, as described earlier for mitochondria and chloroplasts (see Section 7.5.1). It is believed that all peroxisomal membrane proteins, including the putative receptor(s), are imported from the cytosol (Fig. 8-34). Lipids required for the construction of the new peroxisomal membrane are likely delivered from the cytosol as well. They may be transferred from their sites of synthesis in the ER membrane by phospholipid exchange proteins (see Section 8.6.15).

Fig. 8-35. Micrograph of a cultured mammalian cell. In this preparation, proteins retained in the ER are visualized using fluorescently labeled Antibodies. The ER forms a reticular network extending throughout the Cytoplasm, such that virtually any region of the cytosol is closely apposed to some part of the ER membrane. (Courtesy of Hugh Pelham.)

Conclusions

Peroxisomes specialize in carrying out oxidation reactions using molecular oxygen. They produce hydrogen peroxide (which they require for oxidation) and break down its excess using catalase. Like mitochondria and chloroplasts, peroxisomes are believed to be self-replicating organelles. However, they do not contain DNA or ribosomes. It is thought that they include a unique membrane receptor that allows all proteins (including the receptor itself) to be imported into the organelle via selective Transport from the cytosol.