Atlas of plant and animal histology

Peroxisomes are more or less rounded membrane-bound organelles with about 0.1–1 m in diameter. They can be found in all eukaryotic cells and have a salient metabolic role. Sometimes, the concentration of enzymes they contain is so high that the enzymes become crystals.

1. Biogenesis

Peroxisomes are adaptable organelles. They can increase in number and size according to the cellular requirements and be restored to normal levels after they complete their role. They can also modify their repertory of enzymes. Peroxisomes acquire proteins synthesized by cytosolic free ribosomes, and are targeted to either the peroxisome membrane or the interior of the organelle. In the peroxisome membrane, there are proteins known as peroxins, which recognize and transport molecules into peroxisomes or to the peroxisomal membrane. There are 12 peroxin types. Proteins targeted to peroxisomes have amino acid sequences known as PTS1 and PTS2 (peroxisome target sequences), which are recognized by peroxins. Peroxisomal metabolic enzymes are translocated across the peroxisome membrane, but some proteins are targeted to the membrane itself. Unlike other organelles where proteins are acquired in an unfolded manner, folded and even aggregated proteins can be incorporated into peroxisomes. Addition of new molecules makes peroxisomes mature and grow.

The biogenesis of peroxisomes, that is, the formation of new peroxisomes, can be done in two ways: a) growing and division from preexisting peroxisomes, and b) by emerging from the endoplasmic reticulum and mitochondria if there are no peroxisomes in the cell (Figure 1).

a) Peroxisomes may proliferate through growth and strangulation. The fission molecular machinery is similar to that used during the division of mitochondria and chloroplasts, despite their different evolutionary origins. The peroxisome division process begins when the peroxisome membrane contacts the endoplasmic reticulum membranes, which allows lipids to be transferred to the peroxisome membranes. Thus, the peroxisome can enlarge its membrane and get bigger. New peroxisomes are formed by the strangulation of a growing peroxisome. These new peroxisomes mature by incorporating proteins from the cytosol and lipids from the endoplasmic reticulum. The connection between the endoplasmic reticulum and peroxisome may regulate the movement of peroxisomes in the cytoplasm. It has been suggested that the growing of peroxisomes may happen through vesicles coming from the endoplasmic reticulum, but the evidence is weak.

b) If all peroxisomes in a cell are eliminated, a new peroxisome population can be generated from scratch. In mammals, they are formed from vesicles coming from the endoplasmic reticulum (they contain peroxin 16) and from the mitochondria (they contain peroxins 1 and 14). However, in yeasts, all vesicles seem to come from the endoplasmic reticulum. Anyway, these pre-peroxisomal vesicles fuse to one another to form pre-peroxisomes that become functional peroxisomes as they recruit cytosolic enzymes and other types of proteins. It is thought that when peroxisomes are removed, the insertion sequence of cytosolic peroxins searches for membranes to be inserted in, and endoplasmic reticulum and mitochondrial membranes are the most suitable for that. Once inserted, they gather and induce the formation of pre-peroxiomal vesicles.

There are proteins, such as pex30, that localize in the regions of the endoplasmic reticulum where lipid droplets are formed. Intriguingly, these proteins are also found in the places where pre-peroximal vesicles are formed. Thus, it looks like peroxisomes and lipid droplet formation processes share part of the molecular machinery.

Peroxisomes are distributed through the cytoplasm thanks to interactions with microtubules and actin filaments. These interactions also allow them to change the morphology and move the two new peroxisomes away from each other after the division.

Autophagy regulates the number of peroxisomes in the cell. This mechanism is found in every eukaryotic cell, and it is higher under cellular stress.

2. Functions

Peroxidases were the first type of enzyme discovered in this organelle, that is why the name peroxisome. After that, more than 50 types of enzymes have been found in peroxisomes. However, particular repertory of enzymes depend on the cell type and functional state of the cell. Peroxisomes carry out an amazing variety of metabolic reactions.

Peroxisomes perform two main functions: lipid metabolism and protection against peroxides and oxidative radicals. In mammals, peroxisomes catabolize lipids with long fatty acid chains, branched lipids, D-amino acids, polyamines, and they participate in plasminogenesis and the synthesis of some cholesterol precursors. In some yeasts, they facilitated the assimilation of alcohol. Catalase and urate oxidase are common enzymes in peroxisomes. Catalase removes hydrogen peroxide (H₂O₂), which is a product of the oxidative reactions. Oxidative reactions can be generally described as follows:

Hydrogen peroxide is a highly reactive molecule and therefore very toxic. Catalase is able to inactivate hydrogen peroxide:

Peroxisomes cooperate with other organelles in many metabolic pathways (see table below). In plants and fungi, β-oxidation is confined to peroxisomes, whereas in animal cells, β-oxidation is also carried out by mitochondria. In the liver, peroxisomes are important for synthesizing bile acids. In plants, peroxisomes can reduce products from CO₂ fixation by a process known as photorespiration, where oxygen is consumed and CO₂ is released. In seeds, however, peroxisomes store fatty acids in the endosperm and cotyledons that are transformed into carbohydrates during germination by a metabolic pathway known as the glyoxilate cycle. That is why these peroxisomes are known as glyoxysomes, which can also be found in filamentous fungi. It is noteworthy that when photosynthesis starts after the first leaves have developed, glyoxysomes become normal peroxisomes in the mature cells of the leaves. In trypanosomes, the malaria parasite, glycosomes are a type of peroxisome where glycolysis happens. Recently, peroxisomes have been proposed as intracellular signaling platforms in mammalian cells. The different types of peroxisomes are known together as microbodies.

Recently, peroxisomes have been proposed as intracellular signaling platforms in mammalian cells.

Different metabolic functions of peroxisomes and the eukaryotic type of cell where they are performed (from Smith and Aitchison, 2013).

As mentioned above, peroxisomes are involved in metabolic pathways that are shared with other organelles. Hence, peroxisomes need to interact and communicate with other cell compartments. It can be done by vesicles, lipid transport proteins and membrane contact sites. Vesicles from the endoplasmic reticulum and mitochondria are involved in the formation of new peroxisomes. However, the bulk flux is through channels, transporters and membrane contact sites. For instance, the substrates for fatty acid oxidation enter peroxisomes through ABCD transporters found in the peroxisome membrane. Very long fatty acids are transported by ABCD1 and ABCD2. ABCD3 transports acetyl-CoA and bile acid precursors. Other smaller molecules, such as NDA+, NADH, pyruvate, alpha-ketoglutarate, enter through the PXMP2 channel.

It is currently thought that membrane contact sites are a feature of all membrane-bond compartments. In these sites, membranes are as close as 30 nm, but they do not fuse. In COS cells in culture, 90 % of peroxisomes are very close to endoplasmic reticulum tubules. VAPs are key proteins at these types of membrane contact sites. VAPs are endoplasmic reticulum proteins that recognize peroxisome proteins, such as ACBD4 and ACBD5. About 10-20% of the peroxisomes are in contact with lysosomes. Both organelles cooperate in cholesterol metabolism. A flaw in peroxisome function leads to cholesterol accumulation in lysosomes, which can end up being a pathological process. The contacts between peroxisomes and lipid droplets may transfer lipids toward peroxisome membranes.

• Bibliography ↷

  • Costello JL, Schrader M. 2018. Unloosing the gordian knot of peroxisome formation. Current opinion in cell biology. 50. 50-56.

    Ma C, Agrawal G, Subramani S. 2011. Peroxisome assembly: matrix and membrane protein biogenesis. Journal of cell biology. 193: 7-16.

    Sargsyam, Y, Thoms S. 2020. Staying in healthy contact: how peroxisomes interact with other cell organelles. Trends in molecular medicine. 26: 2.

    Smith JJ, Aitchison JD. 2013. Peroxisomes take shape. Nature reviews in molecular and cell biology. 14. 803-817.