Peroxisome

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Basic structure of a peroxisome

Electron micrograph of a section of a liver cell showing glycogen deposits as accumulations of electron dense particles (arrows). The dark structure with a dense core is a peroxisome. Mitochondria are also shown. x30,000.
Basic Histology, 11th ed, p49

Peroxisomes are ubiquitous organelles in eukaryotes that function to rid the cell of toxic substances. They have a single lipid bilayer membrane that separates their contents from the cytosol (the internal fluid of the cell) and contains membrane proteins critical for various functions, such as importing proteins into the organelles and aiding in proliferation. Unlike lysosomes, which are formed in the secretory pathway, peroxisomes usually self-replicate by enlarging and then dividing, although there is some indication that new ones may be formed directly. Peroxisomes were discovered by the Belgian cytologist Christian de Duve in 1965.

1 Occurrence and evolution
2 Function
3 Protein import
4 Deficiencies
5 References
6 External links

[edit] Occurrence and evolution

Peroxisomes are found in all eukaryotic cells. Peroxisomes contain enzymes for certain oxidative reactions. Prokaryotes lack peroxisomes, so they are more vulnerable to toxic substances like hydrogen peroxide. Peroxisomes help in the decomposition of biohazardous chemicals. The enzymatic content of peroxisomes varies between species, but the presence of common proteins has been used to suggest an endosymbiotic origin (Lazarow and Fujiki 1985), in other words, that peroxisomes evolved from bacteria that invaded larger cells as parasites, and very gradually evolved a symbiotic relationship. However, this view has been challenged by recent discoveries. For example peroxisome-less mutants can restore peroxisomes upon introduction of the wild-type gene, and peroxisomes have been observed to be formed from the Endoplasmic Reticulum(E.R.). (Hoepfner 2005).

An evolutionary analysis of the peroxisomal proteome (Schlüter et al. 2006, Gabaldón et al. 2006) found homologies between the peroxisomal import machinery and the ERAD pathway in the Endoplasmic Reticulum, and a number of metabolic enzymes that were likely recruited from the mitochondria. All together these results indicate that the peroxisome does not have an endosymbiotic origin; instead it likely originates from the E.R. and its proteins were recruited from pools existing within the primitive eukaryote.

[edit] Function

Peroxisomes contain oxidative enzymes, such as catalase, D-amino acid oxidase and uric acid oxidase.^[1] Certain enzymes within the peroxisome, by using molecular oxygen, remove hydrogen atoms from specific organic substrates (labeled as R), in an oxidative reaction, producing hydrogen peroxide (H₂O₂, itself toxic):

$\mathrm{RH}_\mathrm{2} + \mathrm{O}_\mathrm{2} \rightarrow \mathrm{R }+ \mathrm{H}_2\mathrm{O}_2$

Catalase, another enzyme in the peroxisome, in turn uses this H₂O₂ to oxidize other substrates, including phenols, formic acid, formaldehyde and alcohol, by means of the peroxidation reaction:

$\mathrm{H}_2\mathrm{O}_2 + \mathrm{R'H}_2 \rightarrow \mathrm{R'} + 2\mathrm{H}_2\mathrm{O}$ , thus eliminating the poisonous hydrogen peroxide in the process.

This reaction is important in liver and kidney cells where the peroxisomes detoxifiy various toxic substances that enter the blood. About 25% of the ethanol we drink is oxidized to acetaldehyde in this way. In addition, when excess H₂O₂ accumulates in the cell, catalase converts it to H₂O through this reaction:

$2\mathrm{H}_2\mathrm{O}_2 \rightarrow 2\mathrm{H}_2\mathrm{O} + \mathrm{O}_2$

A major function of the peroxisome is the breakdown of fatty acid molecules, in a process called beta-oxidation. In this process, the fatty acids are broken down two carbons at a time, converted to Acetyl-CoA, which is then transported back to the cytosol for further use. In animal cells, beta-oxidation can also occur in the mitochondria. In yeast and plant cells this process is exclusive for the peroxisome.

The first reactions in the formation of plasmalogen in animal cells also occurs in peroxisomes. Plasmalogen is the most abundant phospholipid in myelin. Deficiency of plasmalogens causes profound abnormalities in the myelination of nerve cells, which is one of the reasons that many peroxisomal disorders lead to neurological disease.

Peroxisomes also play a role in the production of bile acids.

[edit] Protein import

Proteins are selectively imported into peroxisomes. Since the organelles contain no DNA or ribosomes and thus have no means of producing proteins, all of their proteins must be imported across the membrane. It is believed that proteins do not transit through the endoplasmic reticulum to get to the peroxisome.

A specific protein signal (PTS or peroxisomal targeting signal) of three amino acids at the C-terminus of many peroxisomal proteins signals the membrane of the peroxisome to import them into the organelle. Other peroxisomal proteins contain a signal at the N-terminus. There are at least 32 known peroxisomal proteins, called peroxins, which participate in the process of importing proteins by means of ATP hydrolysis. Proteins do not have to unfold to be imported into the peroxisome. The protein receptors, the peroxins Pex5 and Pex7, accompany their cargoes (containing a PTS1 or a PTS2, respectively) all the way into the peroxisome where they release the cargo and then return to the cytosol - a step named "recycling". Overall, the import cycle is referred to as the "extended shuttle mechanism". Evidence now indicates that ATP hydrolysis is required for the recycling of receptors to the cytosol. Also, ubiquitination appears to be crucial for the export of PEX5 from the peroxisome, to the cytosol. Little is know about the import of PEX7, although it has helper proteins that have been shown to be ubiquitinated.

[edit] Deficiencies

A deficiency in the protein import can lead to empty peroxisomes, leading to abnormalities in the brain, called Zellweger syndrome. A deficiency in the peroxin Pex2 has shown to be responsible for one form of the syndrome. A milder inherited disease is caused by a defective receptor for the N-terminal import signal. Deficiency of the formation of plasmalogens can also cause severe brain disorders, leading to neurological disease.

[edit] References

^ del Río L, Sandalio L, Palma J, Bueno P, Corpas F (1992). "Metabolism of oxygen radicals in peroxisomes and cellular implications". Free Radic Biol Med 13 (5): 557-80. PMID 1334030.

Gabaldón, T.; et.al. (2006). "Origin and evolution of the peroxisomal proteome". Biology Direct 1 (1): 8.
Hoepfner, D.; et.al. (2005). "Contribution of the Endoplasmic Reticulum to peroxisome formation". Cell 122 (1): 85–95.
Lazarow, P.B.; Fujiki (1985). "Biogenesis of peroxisomes". Ann. Rev. Cell Biol. (1): 489-530.
Leon, S.; et al. (2006). "Dynamics of the peroxisomal import cycle of PpPex20p: ubiquitin-dependent localization and regulation". J. Cell Biol. 172 (1): 67-78.