Peroxisomes (microbodies) were first described by a Swedish doctoral student, J. Rhodin in 1954.[7] They were identified as organelles byChristian de Duve and Pierre Baudhuin in 1966.[8] De Duve and co-workers discovered that peroxisomes contain several oxidases involved in the production of hydrogen peroxide (H2O2) as well ascatalase involved in the decomposition of H2O2 to oxygen and water.[9] Due to their role in peroxide metabolism, De Duve named them "peroxisomes", replacing the formerly used morphological term "microbodies". Later, it was described thatfirefly luciferase is targeted to peroxisomes in mammalian cells, allowing the discovery of the importtargeting signal for peroxisomes, and triggering many advances in the peroxisome biogenesis field.[10][11]
Peroxisomes are small (0.1–1 μm diameter)organelles with a fine, granular matrix, surrounded by a singlebiomembrane located in the cytoplasm of a cell.[12][13] Compartmentalization creates an optimized environment to promote various metabolic reactions within peroxisomes required to sustain cellular functions and viability of the organism.
The number, size, and protein composition of peroxisomes are variable and depend on cell type and environmental conditions. For example, in baker's yeast (S. cerevisiae), it has been observed that, with a good glucose supply, only a few, small peroxisomes are present. In contrast, when the yeasts were supplied with long-chain fatty acids as sole carbon source up to 20 to 25 large peroxisomes can be formed.[14]
A major function of the peroxisome is the breakdown ofvery long chain fatty acids throughbeta oxidation. In animal cells, the long fatty acids are converted tomedium chain fatty acids, which are subsequently shuttled tomitochondria where they eventually are broken down to carbon dioxide and water. In yeast and plant cells, this process is carried out exclusively in peroxisomes.[15][16]
The first reactions in the formation ofplasmalogen in animal cells also occur in peroxisomes. Plasmalogen is the most abundant phospholipid inmyelin. Deficiency of plasmalogens causes profound abnormalities in the myelination ofnerve cells, which is one reason why manyperoxisomal disorders affect the nervous system.[15] Peroxisomes also play a role in the production ofbile acids important for the absorption of fats and fat-soluble vitamins, such as vitamins A and K. Skin disorders are features of genetic disorders affecting peroxisome function as a result.[16]
The specific metabolic pathways that occur exclusively in mammalian peroxisomes are:[4]
β-oxidation of very-long-chain and polyunsaturated fatty acids
biosynthesis of plasmalogens
conjugation of cholic acid as part of bile acid synthesis
Peroxisomes contain oxidativeenzymes, such asD-amino acid oxidase anduric acid oxidase.[17] However the last enzyme is absent in humans, explaining the disease known asgout, caused by the accumulation of uric acid. Certain enzymes within the peroxisome, by using molecular oxygen, remove hydrogen atoms from specific organic substrates (labeled as R), in an oxidative reaction, producinghydrogen peroxide (H2O2, itself toxic):
Catalase, another peroxisomal enzyme, uses this H2O2 to oxidize other substrates, includingphenols,formic acid,formaldehyde, andalcohol, by means of the peroxidation reaction:
, thus eliminating the poisonous hydrogen peroxide in the process.
This reaction is important in liver and kidney cells, where the peroxisomes detoxify various toxic substances that enter the blood. About 25% of theethanol that humans consume by drinking alcoholic beverages is oxidized toacetaldehyde in this way.[15] In addition, when excess H2O2 accumulates in the cell, catalase converts it to H2O through this reaction:
In higher plants, peroxisomes contain also a complex battery of antioxidative enzymes such assuperoxide dismutase, the components of theascorbate-glutathione cycle, and the NADP-dehydrogenases of the pentose-phosphate pathway. It has been demonstrated that peroxisomes generatesuperoxide (O2•−) andnitric oxide (•NO) radicals.[18][19]
There is evidence now that those reactive oxygen species including peroxisomal H2O2 are also important signaling molecules in plants and animals and contribute to healthy aging and age-related disorders in humans.[20]
The peroxisome of plant cells is polarised when fighting fungal penetration. Infection causes aglucosinolate molecule to play an antifungal role to be made and delivered to the outside of the cell through the action of the peroxisomal proteins (PEN2 and PEN3).[21]
Peroxisomes in mammals and humans also contribute to anti-viral defense.[22] and the combat of pathogens[23]
Peroxisomes are derived from thesmooth endoplasmic reticulum under certain experimental conditions and replicate by membrane growth and division out of pre-existing organelles.[24][25][26] Peroxisome matrix proteins are translated in the cytoplasm prior to import. Specific amino acid sequences (PTS orperoxisomal targeting signal) at theC-terminus (PTS1) orN-terminus (PTS2) of peroxisomal matrix proteins signal them to be imported into the organelle by a targeting factor. There are currently 36 known proteins involved in peroxisome biogenesis and maintenance, calledperoxins,[27] which participate in the process of peroxisome assembly in different organisms. In mammalian cells, there are 13 characterized peroxins. In contrast to protein import into the endoplasmic reticulum (ER) or mitochondria, proteins do not need to be unfolded to be imported into the peroxisome lumen. The matrix protein import receptors, the peroxinsPEX5 andPEX7, accompany their cargoes (containing a PTS1 or a PTS2 amino acid sequence, respectively) all the way to the peroxisome where they release the cargo into the peroxisomal matrix and then return to thecytosol – a step namedrecycling. A special way of peroxisomal protein targeting is called piggybacking. Proteins transported by this unique method do not have a canonical PTS but bind on a PTS protein to be transported as a complex.[28] A model describing the import cycle is referred to as theextended shuttle mechanism.[29] There is now evidence that ATP hydrolysis is required for the recycling of receptors to the cytosol. Also,ubiquitination is crucial for the export of PEX5 from the peroxisome to the cytosol. The biogenesis of the peroxisomal membrane and the insertion of peroxisomal membrane proteins (PMPs) requires the peroxins PEX19, PEX3, and PEX16. PEX19 is a PMP receptor and chaperone, which binds the PMPs and routes them to the peroxisomal membrane, where it interacts with PEX3, a peroxisomal integral membrane protein. PMPs are then inserted into the peroxisomal membrane.
The degradation of peroxisomes is called pexophagy.[30]
The diverse functions of peroxisomes require dynamic interactions and cooperation with many organelles involved in cellular lipid metabolisms such as the endoplasmic reticulum, mitochondria, lipid droplets, and lysosomes.[31]
Peroxisomes interact with mitochondria in several metabolic pathways, including β-oxidation of fatty acids and the metabolism of reactive oxygen species.[4] Both organelles are in close contact with the endoplasmic reticulum and share several proteins, including organelle fission factors.[32] Peroxisomes also interact with the endoplasmic reticulum and cooperate in the synthesis of ether lipids (plasmalogens), which are important for nerve cells (see above). In filamentous fungi, peroxisomes move on microtubules by 'hitchhiking,' a process involving contact with rapidly moving early endosomes.[33] Physical contact between organelles is often mediated by membrane contact sites, where membranes of two organelles are physically tethered to enable rapid transfer of small molecules, enable organelle communication and are crucial for coordination of cellular functions and hence human health.[34] Alterations of membrane contacts have been observed in various diseases.
PEX genes encode the protein machinery (peroxins) required for proper peroxisome assembly. Peroxisomal membrane proteins are imported through at least two routes, one of which depends on the interaction between peroxin 19 and peroxin 3, while the other is required for the import of peroxin 3, either of which may occur without the import of matrix (lumen) enzymes, which possess the peroxisomal targeting signal PTS1 or PTS2 as previously discussed.[37] Elongation of the peroxisome membrane and the final fission of the organelle are regulated by Pex11p.[38]
The protein content of peroxisomes varies across species or organism, but the presence of proteins common to many species has been used to suggest anendosymbiotic origin; that is, peroxisomes evolved from bacteria that invaded larger cells as parasites, and very gradually evolved a symbiotic relationship.[41] However, this view has been challenged by recent discoveries.[42] For example, peroxisome-less mutants can restore peroxisomes upon introduction of the wild-type gene.
Two independent evolutionary analyses of the peroxisomalproteome found homologies between the peroxisomal import machinery and theERAD pathway in theendoplasmic reticulum,[43][44] along with a number of metabolic enzymes that were likely recruited from themitochondria.[44] The peroxisome may have had anActinomycetota origin;[45] however, this is controversial.[46]
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^Costello JL, Passmore JB, Islinger M, Schrader M (2018). "Multi-localized Proteins: The Peroxisome-Mitochondria Connection".Proteomics of Peroxisomes. Subcellular Biochemistry. Vol. 89. pp. 383–415.doi:10.1007/978-981-13-2233-4_17.ISBN978-981-13-2232-7.PMID30378033.
^Fagarasanu A, Fagarasanu M, Rachubinski RA (2007). "Maintaining peroxisome populations: a story of division and inheritance".Annual Review of Cell and Developmental Biology.23:321–44.doi:10.1146/annurev.cellbio.23.090506.123456.PMID17506702.
^Duhita N, Le HA, Satoshi S, Kazuo H, Daisuke M, Takao S (January 2010). "The origin of peroxisomes: The possibility of an actinobacterial symbiosis".Gene.450 (1–2):18–24.doi:10.1016/j.gene.2009.09.014.PMID19818387.
^Gabaldón T, Capella-Gutiérrez S (October 2010). "Lack of phylogenetic support for a supposed actinobacterial origin of peroxisomes".Gene.465 (1–2):61–5.doi:10.1016/j.gene.2010.06.004.PMID20600706.
Effelsberg D, Cruz-Zaragoza LD, Schliebs W, Erdmann R (2016). "Pex9p is a novel yeast peroxisomal import receptor for PTS1-proteins".Journal of Cell Science.129 (21):4057–4066.doi:10.1242/jcs.195271.PMID27678487.
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