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Extensive update with the current knowledge about peroxisomes.
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[[File:Peroxisome in rat neonatal cardiomyocyte.jpg|alt=Peroxisome in rat neonatal cardiomyocyte staining The SelectFX Alexa Fluor 488 Peroxisome Labeling Kit directed against peroxisomal membrane protein 70 (PMP 70)|thumb|Peroxisome in rat neonatal cardiomyocyte]]
[[File:Peroxisome in rat neonatal cardiomyocyte.jpg|alt=Peroxisome in rat neonatal cardiomyocyte staining The SelectFX Alexa Fluor 488 Peroxisome Labeling Kit directed against peroxisomal membrane protein 70 (PMP 70)|thumb|Peroxisome in rat neonatal cardiomyocyte]]


A '''peroxisome''' ({{IPA-all|pɛɜˈɹɒksɪˌsoʊm}})<ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/peroxisome|title=Definition of PEROXISOME|website=www.merriam-webster.com|language=en|access-date=2019-10-30}}</ref> is a type of [[organelle]] known as a [[microbody]], found in virtually all [[eukaryotic]] cells.<ref name="pmid20124343">{{cite journal | vauthors = Gabaldón T | title = Peroxisome diversity and evolution | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 365 | issue = 1541 | pages = 765–73 | date = Mar 2010 | pmid = 20124343 | pmc = 2817229 | doi = 10.1098/rstb.2009.0240 }}</ref> They are involved in [[catabolism]] of [[very long chain fatty acid]]s, [[branched chain fatty acids]], [[D-amino acids]], and [[polyamine]]s, [[redox|reduction]] of [[reactive oxygen species]] – specifically [[hydrogen peroxide]]<ref name="ROS and peroxisomes">{{cite journal | vauthors = Bonekamp NA, Völkl A, Fahimi HD, Schrader M | title = Reactive oxygen species and peroxisomes: struggling for balance | journal = BioFactors | volume = 35 | issue = 4 | pages = 346–55 | pmid = 19459143 | doi = 10.1002/biof.48 | year=2009}}</ref> – and biosynthesis of [[plasmalogens]], i.e., [[ether phospholipid]]s critical for the normal function of mammalian brains and lungs.<ref name="pmid16756494">{{cite journal | vauthors = Wanders RJ, Waterham HR | title = Biochemistry of mammalian peroxisomes revisited | journal = Annual Review of Biochemistry | volume = 75 | issue = | pages = 295–332 | year = 2006 | pmid = 16756494 | doi = 10.1146/annurev.biochem.74.082803.133329 }}</ref> They also contain approximately 10% of the total activity of two enzymes in the [[pentose phosphate pathway]], which is important for energy metabolism.<ref name="pmid16756494"/> It is vigorously debated whether peroxisomes are involved in [[isoprenoid]] and [[cholesterol]] synthesis in animals.<ref name="pmid16756494"/> Other known peroxisomal functions include the [[glyoxylate cycle]] in germinating seeds ("[[glyoxysomes]]"), [[photorespiration]] in leaves,<ref>{{cite book | vauthors = Evert RF, Eichhorn SE | year = 2006 | title = Esau's Plant Anatomy: Meristems, Cells, and Tissues of the Plant Body: Their Structure, Function, and Development|publisher=John Wiley & Sons|isbn=9780471738435}}</ref> [[glycolysis]] in [[trypanosomes]] ("[[glycosome]]s"), and [[methanol]] and/or amine oxidation and assimilation in some [[Yeast|yeasts]].
A '''peroxisome''' ({{IPA-all|pɛɜˈɹɒksɪˌsoʊm}}) <ref>{{Cite web|url=https://www.merriam-webster.com/dictionary/peroxisome|title=Definition of PEROXISOME|website=www.merriam-webster.com|language=en|access-date=2019-10-30}}</ref> is a membrane-bound [[organelle]] (formerly known as a [[microbody]]), found in the cytoplasm of virtually almost all [[eukaryotic]] cells <ref name="pmid20124343">{{cite journal|last=|first=|vauthors=Islinger M, Voelkl A, Fahimi HD, Schrader M|date=Nov 2018|title=The peroxisome: an update on mysteries 2.0|url=|journal=Histochem Cell Biol|volume=150|issue=5|pages=443-471|doi=10.1007/s00418-018-1722-5|pmc=6182659|pmid=30219925|via=}}</ref><ref>{{Cite journal|last=|first=|vauthors=Islinger M, Schrader M|date=Oct 2011|title=Peroxisomes|url=|journal=Curr Biol|volume=21|pages=19|doi=10.1016/j.cub.2011.07.024|pmid=21996497|via=}}</ref>. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which [[hydrogen peroxide]] (H<sub>2</sub>O<sub>2</sub>) is then formed. Peroxisomes owe their name to hydrogen peroxide generating and scavenging activities. They perform key roles in lipid metabolism and the conversion of [[reactive oxygen species]]. Peroxisomes are involved in the [[catabolism]] of [[very long chain fatty acid]]s, [[branched chain fatty acids]], bile acid intermediates (in the liver), [[D-amino acids]], and [[polyamine]]s, the [[redox|reduction]] of [[reactive oxygen species]] – specifically [[hydrogen peroxide]] <ref name="ROS and peroxisomes">{{cite journal | vauthors = Bonekamp NA, Völkl A, Fahimi HD, Schrader M | title = Reactive oxygen species and peroxisomes: struggling for balance | journal = BioFactors | volume = 35 | issue = 4 | pages = 346–55 | pmid = 19459143 | doi = 10.1002/biof.48 | year=2009}}</ref> – and the biosynthesis of [[plasmalogens]], i.e., [[ether phospholipid]]s critical for the normal function of mammalian brains and lungs <ref name="pmid16756494">{{cite journal | vauthors = Wanders RJ, Waterham HR | title = Biochemistry of mammalian peroxisomes revisited | journal = Annual Review of Biochemistry | volume = 75 | issue = | pages = 295–332 | year = 2006 | pmid = 16756494 | doi = 10.1146/annurev.biochem.74.082803.133329 }}</ref>. They also contain approximately 10% of the total activity of two enzymes in the [[pentose phosphate pathway]], which is important for energy metabolism <ref name="pmid16756494" />. It is vigorously debated whether peroxisomes are involved in [[isoprenoid]] and [[cholesterol]] synthesis in animals <ref name="pmid16756494" />. Other known peroxisomal functions include the [[glyoxylate cycle]] in germinating seeds ("[[glyoxysomes]]"), [[photorespiration]] in leaves <ref>{{cite book | vauthors = Evert RF, Eichhorn SE | year = 2006 | title = Esau's Plant Anatomy: Meristems, Cells, and Tissues of the Plant Body: Their Structure, Function, and Development|publisher=John Wiley & Sons|isbn=9780471738435}}</ref>, [[glycolysis]] in [[trypanosomes]] ("[[glycosome]]s"), and [[methanol]] and/or amine oxidation and assimilation in some [[Yeast|yeasts]].


==History==
==History==
Peroxisomes were identified as organelles by the Belgian cytologist [[Christian de Duve]] in 1967<ref name="pmid4389648">{{cite journal | vauthors = de Duve C | title = The peroxisome: a new cytoplasmic organelle | journal = Proceedings of the Royal Society of London. Series B, Biological Sciences | volume = 173 | issue = 1030 | pages = 71–83 | date = Apr 1969 | pmid = 4389648 | doi = 10.1098/rspb.1969.0039 }}</ref> after they had been first described by a Swedish doctoral student, J. Rhodin in 1954.<ref name="Rhodin_1954">{{cite journal | vauthors = Rhodin, J | title = Correlation of ultrastructural organization and function in normal and experimentally changed proximal tubule cells of the mouse kidney | journal = Doctorate Thesis. Karolinska Institutet, Stockholm | volume = | issue = | pages = | year = 1954 | pmid = | doi = }}</ref>
Peroxisomes (microbodies) were first described by a Swedish doctoral student, J. Rhodin in 1954 <ref name="Rhodin_1954">{{cite journal|vauthors=Rhodin, J|year=1954|title=Correlation of ultrastructural organization and function in normal and experimentally changed proximal tubule cells of the mouse kidney|journal=Doctorate Thesis. Karolinska Institutet, Stockholm|volume=|issue=|pages=|doi=|pmid=}}</ref>. They were identified as organelles by the Belgian cytologist [[Christian de Duve]] in 1967 <ref name="pmid4389648">{{cite journal | vauthors = de Duve C | title = The peroxisome: a new cytoplasmic organelle | journal = Proceedings of the Royal Society of London. Series B, Biological Sciences | volume = 173 | issue = 1030 | pages = 71–83 | date = Apr 1969 | pmid = 4389648 | doi = 10.1098/rspb.1969.0039 }}</ref>. De Duve and co-workers discovered that peroxisomes contain several oxidases involved in the production of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), as well as catalase involved in the decomposition of H<sub>2</sub>O<sub>2</sub> to oxygen and water. Due to their role in peroxide metabolism, De Duve named them “peroxisomes”, replacing the formerly used morphological term “microbodies”.

== Structural Design ==
Peroxisomes are small (0.1-1 µm diameter) subcellular compartments (organelles) with a fine, granular matrix and surrounded by a single biomembrane which are located in the cytoplasm of a cell <ref>{{Cite book|url=|title=Karlsons Biochemistry and Pathobiochemistry|last=|first=|vauthors=Karlson, P, Doenecke D, Koolman J, Fuchs G, Gerok W|date=|publisher=Georg Thieme|others=|year=2005|isbn=978-3133578158|edition=15|location=Stuttgart|pages=396f|oclc=181474420}}</ref><ref>{{Cite book|url=https://www.worldcat.org/oclc/180904366|title=Biology of Plants|last=|first=|vauthors=Raven PH, Evert RF, Eichhorn SE|date=|publisher=De Gruyter|others=|year=2006|isbn=978-3-11-018531-7|edition=4|location=Berlin|pages=53f|oclc=180904366}}</ref>. 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 (''[[Saccharomyces cerevisiae|S. cerevisiae]]''), it has been observed that, with 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 <ref>{{Cite book|url=https://www.worldcat.org/oclc/489629727|title=Yeast: Molecular and Cell Biology|last=Feldmann|first=Horst|date=|publisher=Wiley-VCH|year=2009|isbn=978-3527326099|location=Weinheim|pages=159|oclc=489629727}}</ref>.


== Metabolic functions ==
== Metabolic functions ==
A major function of the peroxisome is the breakdown of [[very long chain fatty acid]]s through [[beta oxidation]]. In animal cells, the long fatty acids are converted to [[Medium-chain triglyceride|medium chain fatty acids]], which are subsequently shuttled to [[mitochondria]] where they eventually are broken down to carbon dioxide and water. In yeast and plant cells, this process is carried out exclusively in peroxisomes.<ref name="alberts">{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P | title = Molecular Biology of the Cell | edition = Fourth | publisher = Garland Science | location = New York | year = 2002 | pages = | quote = | isbn = 978-0-8153-3218-3 | chapter = Chapter 12: Peroxisomes | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.2194 | accessdate = }}</ref>
A major function of the peroxisome is the breakdown of [[very long chain fatty acid]]s through [[beta oxidation]]. In animal cells, the long fatty acids are converted to [[Medium-chain triglyceride|medium chain fatty acids]], which are subsequently shuttled to [[mitochondria]] where they eventually are broken down to carbon dioxide and water. In yeast and plant cells, this process is carried out exclusively in peroxisomes <ref name="alberts">{{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P | title = Molecular Biology of the Cell | edition = Fourth | publisher = Garland Science | location = New York | year = 2002 | pages = | quote = | isbn = 978-0-8153-3218-3 | chapter = Chapter 12: Peroxisomes | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.2194 | accessdate = }}</ref>.


The first reactions in the formation of [[plasmalogen]] in animal cells also occur in peroxisomes. Plasmalogen is the most abundant phospholipid in [[myelin]]. Deficiency of plasmalogens causes profound abnormalities in the myelination of [[neuron|nerve cells]], which is one reason why many [[peroxisomal disorders]] affect the nervous system.<ref name="alberts"/> Peroxisomes also play a role in the production of [[bile]] 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.
The first reactions in the formation of [[plasmalogen]] in animal cells also occur in peroxisomes. Plasmalogen is the most abundant phospholipid in [[myelin]]. Deficiency of plasmalogens causes profound abnormalities in the myelination of [[neuron|nerve cells]], which is one reason why many [[peroxisomal disorders]] affect the nervous system <ref name="alberts"/>. Peroxisomes also play a role in the production of [[bile]] 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.

The specific metabolic pathways that occur exclusively in mammalian peroxisomes are <ref name="pmid16756494" />:

* the α-oxidation of phytanic acid

* the β-oxidation of very long-chain and polyunsaturated fatty acids

* the biosynthesis of plasmalogens

* the conjugation of cholic acid as part of bile acid synthesis

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Peroxisomes contain oxidative [[enzyme]]s, such as [[D-amino acid oxidase]] and [[uric acid oxidase]] <ref name="pmid1334030">{{cite journal | vauthors = del Río LA, Sandalio LM, Palma JM, Bueno P, Corpas FJ | title = Metabolism of oxygen radicals in peroxisomes and cellular implications | journal = Free Radical Biology & Medicine | volume = 13 | issue = 5 | pages = 557–80 | date = Nov 1992 | pmid = 1334030 | doi = 10.1016/0891-5849(92)90150-F }}</ref>. However the last enzyme is absent in humans, explaining the disease known as [[gout]], 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, producing [[hydrogen peroxide]] (H<sub>2</sub>O<sub>2</sub>, itself toxic):


⚫
Peroxisomes contain oxidative [[enzyme]]s, such as [[D-amino acid oxidase]] and [[uric acid oxidase]].<ref name="pmid1334030">{{cite journal | vauthors = del Río LA, Sandalio LM, Palma JM, Bueno P, Corpas FJ | title = Metabolism of oxygen radicals in peroxisomes and cellular implications | journal = Free Radical Biology & Medicine | volume = 13 | issue = 5 | pages = 557–80 | date = Nov 1992 | pmid = 1334030 | doi = 10.1016/0891-5849(92)90150-F }}</ref> However the last enzyme is absent in humans, explaining the disease known as [[gout]], 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, producing [[hydrogen peroxide]] (H<sub>2</sub>O<sub>2</sub>, itself toxic):
:<math>\mathrm{RH}_\mathrm{2} + \mathrm{O}_\mathrm{2} \rightarrow \mathrm{R }+ \mathrm{H}_2\mathrm{O}_2</math>
:<math>\mathrm{RH}_\mathrm{2} + \mathrm{O}_\mathrm{2} \rightarrow \mathrm{R }+ \mathrm{H}_2\mathrm{O}_2</math>


Catalase, another peroxisomal enzyme, uses this H<sub>2</sub>O<sub>2</sub> to oxidize other substrates, including [[phenols]], [[formic acid]], [[formaldehyde]], and [[alcohol]], by means of the peroxidation reaction:
Catalase, another peroxisomal enzyme, uses this H<sub>2</sub>O<sub>2</sub> to oxidize other substrates, including [[phenols]], [[formic acid]], [[formaldehyde]], and [[alcohol]], by means of the peroxidation reaction:

:<math>\mathrm{H}_2\mathrm{O}_2 + \mathrm{R'H}_2 \rightarrow \mathrm{R'} + 2\mathrm{H}_2\mathrm{O}</math>, thus eliminating the poisonous hydrogen peroxide in the process.
:<math>\mathrm{H}_2\mathrm{O}_2 + \mathrm{R'H}_2 \rightarrow \mathrm{R'} + 2\mathrm{H}_2\mathrm{O}</math>, 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 the [[ethanol]] alcohol humans drink is oxidized to [[acetaldehyde]] in this way.<ref name="alberts"/> In addition, when excess H<sub>2</sub>O<sub>2</sub> accumulates in the cell, catalase converts it to H<sub>2</sub>O through this reaction:
This reaction is important in liver and kidney cells, where the peroxisomes detoxify various toxic substances that enter the blood. About 25% of the [[ethanol]] that humans consume by drinking alcoholic beverages is oxidized to [[acetaldehyde]] in this way <ref name="alberts"/>. In addition, when excess H<sub>2</sub>O<sub>2</sub> accumulates in the cell, catalase converts it to H<sub>2</sub>O through this reaction:

:<math>2\mathrm{H}_2\mathrm{O}_2 \rightarrow 2\mathrm{H}_2\mathrm{O} + \mathrm{O}_2</math>
:<math>2\mathrm{H}_2\mathrm{O}_2 \rightarrow 2\mathrm{H}_2\mathrm{O} + \mathrm{O}_2</math>


In higher plants, peroxisomes contain also a complex battery of antioxidative enzymes such as superoxide dismutase, the components of the [[ascorbate-glutathione cycle]], and the NADP-dehydrogenases of the pentose-phosphate pathway. It has been demonstrated that peroxisomes generate [[superoxide]] (O<sub>2</sub><sup>•−</sup>) and [[nitric oxide]] (<sup>•</sup>NO) radicals.<ref name="pmid11286918">{{cite journal | vauthors = Corpas FJ, Barroso JB, del Río LA | title = Peroxisomes as a source of reactive oxygen species and nitric oxide signal molecules in plant cells | journal = Trends in Plant Science | volume = 6 | issue = 4 | pages = 145–50 | date = Apr 2001 | pmid = 11286918 | doi = 10.1016/S1360-1385(01)01898-2 }}</ref><ref name="pmid15347796">{{cite journal | vauthors = Corpas FJ, Barroso JB, Carreras A, Quirós M, León AM, Romero-Puertas MC, Esteban FJ, Valderrama R, Palma JM, Sandalio LM, Gómez M, del Río LA | title = Cellular and subcellular localization of endogenous nitric oxide in young and senescent pea plants | journal = Plant Physiology | volume = 136 | issue = 1 | pages = 2722–33 | date = Sep 2004 | pmid = 15347796 | pmc = 523336 | doi = 10.1104/pp.104.042812 }}</ref>
In higher plants, peroxisomes contain also a complex battery of antioxidative enzymes such as superoxide dismutase, the components of the [[ascorbate-glutathione cycle]], and the NADP-dehydrogenases of the pentose-phosphate pathway. It has been demonstrated that peroxisomes generate [[superoxide]] (O<sub>2</sub><sup>•−</sup>) and [[nitric oxide]] (<sup>•</sup>NO) radicals <ref name="pmid11286918">{{cite journal | vauthors = Corpas FJ, Barroso JB, del Río LA | title = Peroxisomes as a source of reactive oxygen species and nitric oxide signal molecules in plant cells | journal = Trends in Plant Science | volume = 6 | issue = 4 | pages = 145–50 | date = Apr 2001 | pmid = 11286918 | doi = 10.1016/S1360-1385(01)01898-2 }}</ref><ref name="pmid15347796">{{cite journal | vauthors = Corpas FJ, Barroso JB, Carreras A, Quirós M, León AM, Romero-Puertas MC, Esteban FJ, Valderrama R, Palma JM, Sandalio LM, Gómez M, del Río LA | title = Cellular and subcellular localization of endogenous nitric oxide in young and senescent pea plants | journal = Plant Physiology | volume = 136 | issue = 1 | pages = 2722–33 | date = Sep 2004 | pmid = 15347796 | pmc = 523336 | doi = 10.1104/pp.104.042812 }}</ref>.


There is evidence now that those reactive oxygen species including peroxisomal H2O2 are also important signalling molecules in plants and animals and contribute to healthy ageing and age-related disorders in humans <ref>{{Cite journal|last=|first=|last2=|last3=|vauthors=Lismont C, Revenco I, Fransen M|date=Jul 2019|title=Peroxisomal Hydrogen Peroxide Metabolism and Signaling in Health and Disease|url=https://www.mdpi.com/1422-0067/20/15/3673|journal=International Journal of Molecular Sciences|language=en|volume=20|issue=15|pages=3673|doi=10.3390/ijms20153673|issn=1422-0067|pmc=PMC6695606|pmid=31357514|via=}}</ref>.
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The peroxisome of plant cells is polarised when fighting fungal penetration. Infection causes a [[glucosinolate]] 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).<ref name="pmid19095900">{{cite journal | vauthors = Bednarek P, Pislewska-Bednarek M, Svatos A, Schneider B, Doubsky J, Mansurova M, Humphry M, Consonni C, Panstruga R, Sanchez-Vallet A, Molina A, Schulze-Lefert P | title = A glucosinolate metabolism pathway in living plant cells mediates broad-spectrum antifungal defense | journal = Science | volume = 323 | issue = 5910 | pages = 101–6 | date = Jan 2009 | pmid = 19095900 | doi = 10.1126/science.1163732 }}</ref>

⚫
The peroxisome of plant cells is polarised when fighting fungal penetration. Infection causes a [[glucosinolate]] 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) <ref name="pmid19095900">{{cite journal | vauthors = Bednarek P, Pislewska-Bednarek M, Svatos A, Schneider B, Doubsky J, Mansurova M, Humphry M, Consonni C, Panstruga R, Sanchez-Vallet A, Molina A, Schulze-Lefert P | title = A glucosinolate metabolism pathway in living plant cells mediates broad-spectrum antifungal defense | journal = Science | volume = 323 | issue = 5910 | pages = 101–6 | date = Jan 2009 | pmid = 19095900 | doi = 10.1126/science.1163732 }}</ref>.

Peroxisomes in mammals and humans also contribute to anti-viral defense and the combat of pathogens <ref>{{Cite journal|last=|first=|vauthors=Di Cara F, Bülow MH, Simmonds AJ, Rachubinski RA|date=Nov 2018|editor-last=|editor-first=|title=Dysfunctional peroxisomes compromise gut structure and host defense by increased cell death and Tor-dependent autophagy|url=https://www.molbiolcell.org/doi/10.1091/mbc.E18-07-0434|journal=Molecular Biology of the Cell|language=en|volume=29|issue=22|pages=2766–2783|doi=10.1091/mbc.E18-07-0434|issn=1059-1524|pmc=PMC6249834|pmid=30188767|via=}}</ref>.


== Peroxisome assembly ==
== Peroxisome assembly ==
Peroxisomes can be derived from the [[endoplasmic reticulum]] and replicate by fission.<ref name="pmid16009135">{{cite journal | vauthors = Hoepfner D, Schildknegt D, Braakman I, Philippsen P, Tabak HF | title = Contribution of the endoplasmic reticulum to peroxisome formation | journal = Cell | volume = 122 | issue = 1 | pages = 85–95 | date = Jul 2005 | pmid = 16009135 | doi = 10.1016/j.cell.2005.04.025 | url = http://dspace.library.uu.nl:8080/handle/1874/9833 }}</ref> Peroxisome matrix proteins are translated in the cytoplasm prior to import. Specific amino acid sequences (PTS or [[peroxisomal targeting signal]]) at the ''[[C-terminus]]'' (PTS1) or ''[[N-terminus]]'' (PTS2) of peroxisomal matrix proteins signals them to be imported into the organelle. There are at least 32 known peroxisomal proteins, called [[peroxin]]s,<ref name="pmid17050007">{{cite journal | vauthors = Saleem RA, Smith JJ, Aitchison JD | title = Proteomics of the peroxisome | journal = Biochimica et Biophysica Acta | volume = 1763 | issue = 12 | pages = 1541–51 | date = Dec 2006 | pmid = 17050007 | pmc = 1858641 | doi = 10.1016/j.bbamcr.2006.09.005 }}</ref> which participate in the process of peroxisome assembly. 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 amino acid sequence, respectively) all the way into the peroxisome where they release the cargo and then return to the [[cytosol]] – a step named ''recycling''. A model describing the import cycle is referred to as the ''extended shuttle mechanism''.<ref name="pmid11336669">{{cite journal | vauthors = Dammai V, Subramani S | title = The human peroxisomal targeting signal receptor, Pex5p, is translocated into the peroxisomal matrix and recycled to the cytosol | journal = Cell | volume = 105 | issue = 2 | pages = 187–96 | date = Apr 2001 | pmid = 11336669 | doi = 10.1016/s0092-8674(01)00310-5 }}</ref> There is now evidence 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.
Peroxisomes can be derived from the [[endoplasmic reticulum]] under certain experimental conditions and replicate by membrane growth and division out of pre-existing organelles <ref name="pmid16009135">{{cite journal | vauthors = Hoepfner D, Schildknegt D, Braakman I, Philippsen P, Tabak HF | title = Contribution of the endoplasmic reticulum to peroxisome formation | journal = Cell | volume = 122 | issue = 1 | pages = 85–95 | date = Jul 2005 | pmid = 16009135 | doi = 10.1016/j.cell.2005.04.025 | url = http://dspace.library.uu.nl:8080/handle/1874/9833 }}</ref><ref>{{Cite journal|vauthors=Schrader M, Costello JL, Godinho LF, Azadi AS, Islinger M|date=May 2016|title=Proliferation and fission of peroxisomes — An update|url=http://dx.doi.org/10.1016/j.bbamcr.2015.09.024|journal=Biochimica et Biophysica Acta (BBA) - Molecular Cell Research|volume=1863|issue=5|pages=971–983|doi=10.1016/j.bbamcr.2015.09.024|issn=0167-4889|via=}}</ref><ref>{{Cite journal|last=|first=|vauthors=Lazarow PB, Fujiki Y|date=Nov 1985|title=Biogenesis of Peroxisomes|url=http://www.annualreviews.org/doi/10.1146/annurev.cb.01.110185.002421|journal=Annual Review of Cell Biology|language=en|volume=1|issue=1|pages=489–530|doi=10.1146/annurev.cb.01.110185.002421|issn=0743-4634|pmid=3916321|via=}}</ref>. Peroxisome matrix proteins are translated in the cytoplasm prior to import. Specific amino acid sequences (PTS or [[peroxisomal targeting signal]]) at the ''[[C-terminus]]'' (PTS1) or ''[[N-terminus]]'' (PTS2) of peroxisomal matrix proteins signals them to be imported into the organelle by a targeting factor. There are currently 36 known proteins involved in peroxisome biogenesis and maintenance, called [[peroxin]]s <ref name="pmid17050007">{{cite journal | vauthors = Saleem RA, Smith JJ, Aitchison JD | title = Proteomics of the peroxisome | journal = Biochimica et Biophysica Acta | volume = 1763 | issue = 12 | pages = 1541–51 | date = Dec 2006 | pmid = 17050007 | pmc = 1858641 | doi = 10.1016/j.bbamcr.2006.09.005 }}</ref>, 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 receptors, the peroxins [[PEX5]] and [[PEX7]], 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 the [[cytosol]] – a step named ''recycling''. A special way of peroxisomal protein targeting is called piggy backing. Proteins that are transported by this unique method, do not have a canonical PTS, but rather bind on a PTS protein to be transported as a complex. A model describing the import cycle is referred to as the ''extended shuttle mechanism'' <ref name="pmid11336669">{{cite journal | vauthors = Dammai V, Subramani S | title = The human peroxisomal targeting signal receptor, Pex5p, is translocated into the peroxisomal matrix and recycled to the cytosol | journal = Cell | volume = 105 | issue = 2 | pages = 187–96 | date = Apr 2001 | pmid = 11336669 | doi = 10.1016/s0092-8674(01)00310-5 }}</ref>. 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 <ref>{{Cite journal|last=Eberhart|first=T|last2=Kovacs|first2=WJ|date=Nov 2018|title=Pexophagy in yeast and mammals: an update on mysteries|url=http://link.springer.com/10.1007/s00418-018-1724-3|journal=Histochemistry and Cell Biology|language=en|volume=150|issue=5|pages=473–488|doi=10.1007/s00418-018-1724-3|issn=0948-6143|via=}}</ref>.

== Peroxisome interaction and communication ==
The diverse functions of peroxisomes require dynamic interactions and cooperation with many organelles involved in cellular lipid metabolism such as the endoplasmic reticulum (ER), mitochondria, lipid droplets, and lysosomes <ref>{{Cite journal|last=Shai|first=N|last2=Schuldiner|first2=M|last3=Zalckvar|first3=E|date=May 2016|title=No peroxisome is an island — Peroxisome contact sites|url=http://dx.doi.org/10.1016/j.bbamcr.2015.09.016|journal=Biochimica et Biophysica Acta (BBA) - Molecular Cell Research|volume=1863|issue=5|pages=1061–1069|doi=10.1016/j.bbamcr.2015.09.016|issn=0167-4889|via=}}</ref>.

Peroxisomes interact with mitochondria in several metabolic pathways, including β-oxidation of fatty acids and the metabolism of reactive oxygen species <ref name="pmid16756494" />. Both organelles are in close contact with the endoplasmic reticulum (ER) and share several proteins, including organelle fission factors <ref>{{Cite journal|last=|first=|vauthors=Costello JL, Passmore JB, Islinger M, Schrader M|date=2018|title=Multi-localized Proteins: The Peroxisome-Mitochondria Connection|url=|journal=Subcell Biochem|volume=89|pages=383-415|doi=10.1007/978-981-13-2233-4_17|pmid=30378033|via=}}</ref>. Peroxisomes also interact with the endoplasmic reticulum (ER) and cooperate in the synthesis of ether lipids (plasmalogens) which are important for nerve cells (see above). 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 <ref>{{Cite journal|last=Castro|first=IG|last2=Schuldiner|first2=M|last3=Zalckvar|first3=E|date=Mar 2018|title=Mind the Organelle Gap – Peroxisome Contact Sites in Disease|url=http://dx.doi.org/10.1016/j.tibs.2018.01.001|journal=Trends in Biochemical Sciences|volume=43|issue=3|pages=199–210|doi=10.1016/j.tibs.2018.01.001|issn=0968-0004|via=}}</ref>. Alterations of membrane contacts have been observed in various diseases.


== Associated medical conditions ==
== Associated medical conditions ==
[[Peroxisomal disorders]] are a class of medical conditions that typically affect the human nervous system as well as many other organ systems. Two common examples are [[X-linked]] [[adrenoleukodystrophy]] and [[peroxisome biogenesis disorders]].<ref name="pmid12740827">{{cite journal | vauthors = Depreter M, Espeel M, Roels F | title = Human peroxisomal disorders | journal = Microscopy Research and Technique | volume = 61 | issue = 2 | pages = 203–23 | date = Jun 2003 | pmid = 12740827 | doi = 10.1002/jemt.10330 }}</ref><ref name="Roels_1995">{{cite journal | vauthors = Depreter M, Espeel M, Roels F | title = Human peroxisomal disorders | journal = Microscopy Research and Technique | volume = 61 | issue = 2 | pages = 203–23 | date = Jun 2003 | pmid = 12740827 | doi = 10.1002/jemt.10330 | url = http://www.springerlink.com/content/0141-8955/18/s1/ }}</ref>
[[Peroxisomal disorders]] are a class of medical conditions that typically affect the human nervous system as well as many other organ systems. Two common examples are [[Adrenoleukodystrophy|X-linked adrenoleukodystrophy]] and [[peroxisome biogenesis disorders]] <ref name="pmid12740827">{{cite journal | vauthors = Depreter M, Espeel M, Roels F | title = Human peroxisomal disorders | journal = Microscopy Research and Technique | volume = 61 | issue = 2 | pages = 203–23 | date = Jun 2003 | pmid = 12740827 | doi = 10.1002/jemt.10330 }}</ref><ref name="Roels_1995">{{cite journal | vauthors = Depreter M, Espeel M, Roels F | title = Human peroxisomal disorders | journal = Microscopy Research and Technique | volume = 61 | issue = 2 | pages = 203–23 | date = Jun 2003 | pmid = 12740827 | doi = 10.1002/jemt.10330 | url = http://www.springerlink.com/content/0141-8955/18/s1/ }}</ref>.


== Genes ==
== Genes ==
''PEX'' genes encode the protein machinery ("peroxins") required for proper peroxisome assembly, as described above. Membrane assembly and maintenance requires three of these (peroxins 3, 16, and 19) and may occur without the import of the matrix (lumen) enzymes. Proliferation of the organelle is regulated by Pex11p.
''PEX'' genes encode the protein machinery ("peroxins") required for proper peroxisome assembly, as described above. Membrane assembly and maintenance requires three of these (peroxins 3, 16, and 19) and may occur without the import of the matrix (lumen) enzymes. Proliferation of the organelle is regulated by Pex11p.


Genes that encode peroxin proteins include: [[PEX1]], [[PEX2]] (PXMP3), [[PEX3]], [[PEX5]], [[PEX6]], [[PEX7]], [[PEX10]], [[PEX11A]], [[PEX11B]], [[PEX11G]], [[PEX12]], [[PEX13]], [[PEX14]], [[PEX16]], [[PEX19]], [[PEX26]], [[PEX28]], [[PEX30]], and [[PEX31]].
Genes that encode peroxin proteins include: [[PEX1]], [[PEX2]] (PXMP3), [[PEX3]], [[PEX5]], [[PEX6]], [[PEX7]], PEX9, [[PEX10]], [[PEX11A]], [[PEX11B]], [[PEX11G]], [[PEX12]], [[PEX13]], [[PEX14]], [[PEX16]], [[PEX19]], [[PEX26]], [[PEX28]], [[PEX30]], and [[PEX31]].


== Evolutionary origins ==
== Evolutionary origins ==
The protein content of peroxisomes varies across species or organism, but the presence of proteins common to many species has been used to suggest an [[Endosymbiotic theory|endosymbiotic]] origin; that is, peroxisomes evolved from bacteria that invaded larger cells as parasites, and very gradually evolved a symbiotic relationship.<ref name="pmid3916321">{{cite journal | vauthors = Lazarow PB, Fujiki Y | title = Biogenesis of peroxisomes | journal = Annual Review of Cell Biology | volume = 1 | issue = | pages = 489–530 | year = 1985 | pmid = 3916321 | doi = 10.1146/annurev.cb.01.110185.002421 }}</ref> However, this view has been challenged by recent discoveries.<ref name="pmid17506702">{{cite journal | vauthors = Fagarasanu A, Fagarasanu M, Rachubinski RA | title = Maintaining peroxisome populations: a story of division and inheritance | journal = Annual Review of Cell and Developmental Biology | volume = 23 | issue = | pages = 321–44 | year = 2007 | pmid = 17506702 | doi = 10.1146/annurev.cellbio.23.090506.123456 }}</ref> For example, peroxisome-less mutants can restore peroxisomes upon introduction of the wild-type gene.
The protein content of peroxisomes varies across species or organism, but the presence of proteins common to many species has been used to suggest an [[Endosymbiotic theory|endosymbiotic]] origin; origin; that is, peroxisomes evolved from bacteria that invaded larger cells as parasites, and very gradually evolved a symbiotic relationship <ref name="pmid3916321">{{cite journal | vauthors = Lazarow PB, Fujiki Y | title = Biogenesis of peroxisomes | journal = Annual Review of Cell Biology | volume = 1 | issue = | pages = 489–530 | year = 1985 | pmid = 3916321 | doi = 10.1146/annurev.cb.01.110185.002421 }}</ref>. However, this view has been challenged by recent discoveries <ref name="pmid17506702">{{cite journal | vauthors = Fagarasanu A, Fagarasanu M, Rachubinski RA | title = Maintaining peroxisome populations: a story of division and inheritance | journal = Annual Review of Cell and Developmental Biology | volume = 23 | issue = | pages = 321–44 | year = 2007 | pmid = 17506702 | doi = 10.1146/annurev.cellbio.23.090506.123456 }}</ref>. For example, peroxisome-less mutants can restore peroxisomes upon introduction of the wild-type gene.


Two independent evolutionary analyses of the peroxisomal [[proteome]] found homologies between the peroxisomal import machinery and the [[Endoplasmic Reticulum Associated Protein Degradation|ERAD]] pathway in the [[endoplasmic reticulum]],<ref name="pmid16452116">{{cite journal | vauthors = Schlüter A, Fourcade S, Ripp R, Mandel JL, Poch O, Pujol A | title = The evolutionary origin of peroxisomes: an ER-peroxisome connection | journal = Molecular Biology and Evolution | volume = 23 | issue = 4 | pages = 838–45 | date = Apr 2006 | pmid = 16452116 | doi = 10.1093/molbev/msj103 }}</ref><ref name="pmid16556314">{{cite journal | vauthors = Gabaldón T, Snel B, van Zimmeren F, Hemrika W, Tabak H, Huynen MA | title = Origin and evolution of the peroxisomal proteome | journal = Biology Direct | volume = 1 | issue = | pages = 8 | year = 2006 | pmid = 16556314 | pmc = 1472686 | doi = 10.1186/1745-6150-1-8 }}</ref> along with a number of metabolic enzymes that were likely recruited from the [[mitochondria]].<ref name="pmid16556314"/> Recently, it has been suggested that the peroxisome may have had an [[actinobacteria]]l origin,<ref name="pmid19818387">{{cite journal | vauthors = Duhita N, Le HA, Satoshi S, Kazuo H, Daisuke M, Takao S | title = The origin of peroxisomes: The possibility of an actinobacterial symbiosis | journal = Gene | volume = 450 | issue = 1–2 | pages = 18–24 | date = Jan 2010 | pmid = 19818387 | doi = 10.1016/j.gene.2009.09.014 }}</ref> however, this is controversial.<ref name="pmid20600706">{{cite journal | vauthors = Gabaldón T, Capella-Gutiérrez S | title = Lack of phylogenetic support for a supposed actinobacterial origin of peroxisomes | journal = Gene | volume = 465 | issue = 1–2 | pages = 61–5 | date = Oct 2010 | pmid = 20600706 | doi = 10.1016/j.gene.2010.06.004 }}</ref>
Two independent evolutionary analyses of the peroxisomal [[proteome]] found homologies between the peroxisomal import machinery and the [[Endoplasmic Reticulum Associated Protein Degradation|ERAD]] pathway in the [[endoplasmic reticulum]] <ref name="pmid16452116">{{cite journal | vauthors = Schlüter A, Fourcade S, Ripp R, Mandel JL, Poch O, Pujol A | title = The evolutionary origin of peroxisomes: an ER-peroxisome connection | journal = Molecular Biology and Evolution | volume = 23 | issue = 4 | pages = 838–45 | date = Apr 2006 | pmid = 16452116 | doi = 10.1093/molbev/msj103 }}</ref><ref name="pmid16556314">{{cite journal | vauthors = Gabaldón T, Snel B, van Zimmeren F, Hemrika W, Tabak H, Huynen MA | title = Origin and evolution of the peroxisomal proteome | journal = Biology Direct | volume = 1 | issue = | pages = 8 | year = 2006 | pmid = 16556314 | pmc = 1472686 | doi = 10.1186/1745-6150-1-8 }}</ref>, along with a number of metabolic enzymes that were likely recruited from the [[mitochondria]] <ref name="pmid16556314" />. Recently, it has been suggested that the peroxisome may have had an [[actinobacteria]]l origin <ref name="pmid19818387">{{cite journal | vauthors = Duhita N, Le HA, Satoshi S, Kazuo H, Daisuke M, Takao S | title = The origin of peroxisomes: The possibility of an actinobacterial symbiosis | journal = Gene | volume = 450 | issue = 1–2 | pages = 18–24 | date = Jan 2010 | pmid = 19818387 | doi = 10.1016/j.gene.2009.09.014 }}</ref>, however, this is controversial <ref name="pmid20600706">{{cite journal | vauthors = Gabaldón T, Capella-Gutiérrez S | title = Lack of phylogenetic support for a supposed actinobacterial origin of peroxisomes | journal = Gene | volume = 465 | issue = 1–2 | pages = 61–5 | date = Oct 2010 | pmid = 20600706 | doi = 10.1016/j.gene.2010.06.004 }}</ref>.


== Other related organelles ==
== Other related organelles ==

Revision as of 12:07, 5 November 2019

Basic structure of a peroxisome
Distribution of peroxisomes (white) in HEK 293 cells during mitosis
Peroxisome in rat neonatal cardiomyocyte staining The SelectFX Alexa Fluor 488 Peroxisome Labeling Kit directed against peroxisomal membrane protein 70 (PMP 70)
Peroxisome in rat neonatal cardiomyocyte

A peroxisome (IPA: [pɛɜˈɹɒksɪˌsoʊm]) [1] is a membrane-bound organelle (formerly known as a microbody), found in the cytoplasm of virtually almost all eukaryotic cells [2][3]. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen peroxide (H2O2) is then formed. Peroxisomes owe their name to hydrogen peroxide generating and scavenging activities. They perform key roles in lipid metabolism and the conversion of reactive oxygen species. Peroxisomes are involved in the catabolism of very long chain fatty acids, branched chain fatty acids, bile acid intermediates (in the liver), D-amino acids, and polyamines, the reduction of reactive oxygen species – specifically hydrogen peroxide [4] – and the biosynthesis of plasmalogens, i.e., ether phospholipids critical for the normal function of mammalian brains and lungs [5]. They also contain approximately 10% of the total activity of two enzymes in the pentose phosphate pathway, which is important for energy metabolism [5]. It is vigorously debated whether peroxisomes are involved in isoprenoid and cholesterol synthesis in animals [5]. Other known peroxisomal functions include the glyoxylate cycle in germinating seeds ("glyoxysomes"), photorespiration in leaves [6], glycolysis in trypanosomes ("glycosomes"), and methanol and/or amine oxidation and assimilation in some yeasts.

History

Peroxisomes (microbodies) were first described by a Swedish doctoral student, J. Rhodin in 1954 [7]. They were identified as organelles by the Belgian cytologist Christian de Duve in 1967 [8]. De Duve and co-workers discovered that peroxisomes contain several oxidases involved in the production of hydrogen peroxide (H2O2), as well as catalase involved in the decomposition of H2O2 to oxygen and water. Due to their role in peroxide metabolism, De Duve named them “peroxisomes”, replacing the formerly used morphological term “microbodies”.

Structural Design

Peroxisomes are small (0.1-1 µm diameter) subcellular compartments (organelles) with a fine, granular matrix and surrounded by a single biomembrane which are located in the cytoplasm of a cell [9][10]. 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 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 [11].

Metabolic functions

A major function of the peroxisome is the breakdown of very long chain fatty acids through beta oxidation. In animal cells, the long fatty acids are converted to medium chain fatty acids, which are subsequently shuttled to mitochondria where they eventually are broken down to carbon dioxide and water. In yeast and plant cells, this process is carried out exclusively in peroxisomes [12].

The first reactions in the formation of plasmalogen in animal cells also occur 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 reason why many peroxisomal disorders affect the nervous system [12]. Peroxisomes also play a role in the production of bile 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.

The specific metabolic pathways that occur exclusively in mammalian peroxisomes are [5]:

  • the α-oxidation of phytanic acid
  • the β-oxidation of very long-chain and polyunsaturated fatty acids
  • the biosynthesis of plasmalogens
  • the conjugation of cholic acid as part of bile acid synthesis

Peroxisomes contain oxidative enzymes, such as D-amino acid oxidase and uric acid oxidase [13]. However the last enzyme is absent in humans, explaining the disease known as gout, 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, producing hydrogen peroxide (H2O2, itself toxic):

Catalase, another peroxisomal enzyme, uses this H2O2 to oxidize other substrates, including phenols, formic acid, formaldehyde, and alcohol, 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 the ethanol that humans consume by drinking alcoholic beverages is oxidized to acetaldehyde in this way [12]. 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 as superoxide dismutase, the components of the ascorbate-glutathione cycle, and the NADP-dehydrogenases of the pentose-phosphate pathway. It has been demonstrated that peroxisomes generate superoxide (O2•−) and nitric oxide (•NO) radicals [14][15].

There is evidence now that those reactive oxygen species including peroxisomal H2O2 are also important signalling molecules in plants and animals and contribute to healthy ageing and age-related disorders in humans [16].

The peroxisome of plant cells is polarised when fighting fungal penetration. Infection causes a glucosinolate 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) [17].

Peroxisomes in mammals and humans also contribute to anti-viral defense and the combat of pathogens [18].

Peroxisome assembly

Peroxisomes can be derived from the endoplasmic reticulum under certain experimental conditions and replicate by membrane growth and division out of pre-existing organelles [19][20][21]. Peroxisome matrix proteins are translated in the cytoplasm prior to import. Specific amino acid sequences (PTS or peroxisomal targeting signal) at the C-terminus (PTS1) or N-terminus (PTS2) of peroxisomal matrix proteins signals them to be imported into the organelle by a targeting factor. There are currently 36 known proteins involved in peroxisome biogenesis and maintenance, called peroxins [22], 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 receptors, the peroxins PEX5 and PEX7, 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 the cytosol – a step named recycling. A special way of peroxisomal protein targeting is called piggy backing. Proteins that are transported by this unique method, do not have a canonical PTS, but rather bind on a PTS protein to be transported as a complex. A model describing the import cycle is referred to as the extended shuttle mechanism [23]. 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 [24].

Peroxisome interaction and communication

The diverse functions of peroxisomes require dynamic interactions and cooperation with many organelles involved in cellular lipid metabolism such as the endoplasmic reticulum (ER), mitochondria, lipid droplets, and lysosomes [25].

Peroxisomes interact with mitochondria in several metabolic pathways, including β-oxidation of fatty acids and the metabolism of reactive oxygen species [5]. Both organelles are in close contact with the endoplasmic reticulum (ER) and share several proteins, including organelle fission factors [26]. Peroxisomes also interact with the endoplasmic reticulum (ER) and cooperate in the synthesis of ether lipids (plasmalogens) which are important for nerve cells (see above). 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 [27]. Alterations of membrane contacts have been observed in various diseases.

Associated medical conditions

Peroxisomal disorders are a class of medical conditions that typically affect the human nervous system as well as many other organ systems. Two common examples are X-linked adrenoleukodystrophy and peroxisome biogenesis disorders [28][29].

Genes

PEX genes encode the protein machinery ("peroxins") required for proper peroxisome assembly, as described above. Membrane assembly and maintenance requires three of these (peroxins 3, 16, and 19) and may occur without the import of the matrix (lumen) enzymes. Proliferation of the organelle is regulated by Pex11p.

Genes that encode peroxin proteins include: PEX1, PEX2 (PXMP3), PEX3, PEX5, PEX6, PEX7, PEX9, PEX10, PEX11A, PEX11B, PEX11G, PEX12, PEX13, PEX14, PEX16, PEX19, PEX26, PEX28, PEX30, and PEX31.

Evolutionary origins

The protein content of peroxisomes varies across species or organism, but the presence of proteins common to many species has been used to suggest an endosymbiotic origin; origin; that is, peroxisomes evolved from bacteria that invaded larger cells as parasites, and very gradually evolved a symbiotic relationship [30]. However, this view has been challenged by recent discoveries [31]. For example, peroxisome-less mutants can restore peroxisomes upon introduction of the wild-type gene.

Two independent evolutionary analyses of the peroxisomal proteome found homologies between the peroxisomal import machinery and the ERAD pathway in the endoplasmic reticulum [32][33], along with a number of metabolic enzymes that were likely recruited from the mitochondria [33]. Recently, it has been suggested that the peroxisome may have had an actinobacterial origin [34], however, this is controversial [35].

Other related organelles

Other organelles of the microbody family related to peroxisomes include glyoxysomes of plants and filamentous fungi, glycosomes of kinetoplastids,[36] and Woronin bodies of filamentous fungi.

See also

References

  1. ^ "Definition of PEROXISOME". www.merriam-webster.com. Retrieved 2019-10-30.
  2. ^ Islinger M, Voelkl A, Fahimi HD, Schrader M (Nov 2018). "The peroxisome: an update on mysteries 2.0". Histochem Cell Biol. 150 (5): 443–471. doi:10.1007/s00418-018-1722-5. PMC 6182659. PMID 30219925.
  3. ^ Islinger M, Schrader M (Oct 2011). "Peroxisomes". Curr Biol. 21: 19. doi:10.1016/j.cub.2011.07.024. PMID 21996497.
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Further reading

External links

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