Editing Protein targeting (section)

===Peroxisomes===
[[File:Peroxisome Protein Targeting.png|thumb|Generalized Protein Targeting to the Peroxisomal Matrix]]
[[Peroxisome]]s contain a single phospholipid bilayer that surrounds the peroxisomal matrix containing a wide variety of proteins and enzymes that participate in anabolism and catabolism. Peroxisomes are specialized cell organelles that carry out specific oxidative reactions using molecular oxygen. Their primary function is to remove hydrogen atoms from organic molecules, a process that results in the production of [[hydrogen peroxide]] ({{chem2|H2O2}}).<ref name="Alberts B, Johnson A, Lewis J-2002" /><ref name="Lodish-2008" /> Within peroxisomes, an enzyme called [[catalase]] plays a critical role. It uses the hydrogen peroxide generated in the earlier reaction to oxidize various other substances, including [[phenols]], [[formic acid]], [[formaldehyde]], and alcohol.<ref name="Alberts B, Johnson A, Lewis J-2002" /><ref name="Lodish-2008" /> This is known as the "peroxidative" reaction.<ref name="Lodish-2008" />

Peroxisomes are particularly important in liver and kidney cells for detoxifying harmful substances that enter the bloodstream. For example, they are responsible for oxidizing about 25% of the [[ethanol]] we consume into [[acetaldehyde]].<ref name="Alberts B, Johnson A, Lewis J-2002" /> Additionally, catalase within peroxisomes can break down excess hydrogen peroxide into water and oxygen and thus preventing potential damage from the build-up of {{chem2|H2O2}}.<ref name="Alberts B, Johnson A, Lewis J-2002" /><ref name="Lodish-2008" /> Since it contains no internal DNA like that of the mitochondria or chloroplast all [[peroxisome|peroxisomal]] proteins are encoded by nuclear genes.<ref>{{Cite book|url=https://www.worldcat.org/oclc/828743403|title=Encyclopedia of biological chemistry|others=Lennarz, William J.,, Lane, M. Daniel|date=8 January 2013|isbn=978-0-12-378631-9|edition=Second|location=London|oclc=828743403}}</ref> To date there are two types of known [[Peroxisomal targeting signal|Peroxisome Targeting Signals]] (PTS):

# '''Peroxisome targeting signal 1 (PTS1)''': a C-terminal tripeptide with a consensus sequence (S/A/C)-(K/R/H)-(L/A). The most common PTS1 is [[serine]]-[[lysine]]-[[leucine]] (SKL).<ref name="Alberts B, Johnson A, Lewis J-2002">{{Cite book |last=Alberts B, Johnson A, Lewis J |title=Molecular Biology of the Cell |publisher=Garland Science |year=2002 |edition=4th |location=New York, NY}}</ref> The initial research that led to the discovery of this consensus observed that when firefly luciferase was expressed in cultured insect cells it was targeted to the peroxisome. By testing a variety of mutations in the gene encoding the expressed [[luciferase]], the consensus sequence was then determined.<ref>{{Cite journal |last=Keller G, Gould S, Deluca M, Subramani S |date=1987 |title=Firefly luciferase is targeted to peroxisomes in mammalian cells |journal=Proceedings of the National Academy of Sciences |volume=84 |issue=10 |pages=3264–3268 |doi=10.1073/pnas.84.10.3264 |pmid=3554235 |pmc=304849 |bibcode=1987PNAS...84.3264K |doi-access=free }}</ref> It has also been found that by adding this C-terminal sequence of SKL to a cytosolic protein that it becomes targeted for transport to the peroxisome. The majority of peroxisomal matrix proteins possess this PTS1 type signal.
# '''Peroxisome targeting signal 2 (PTS2)''': a nonapeptide located near the N-terminus with a consensus sequence (R/K)-(L/V/I)-XXXXX-(H/Q)-(L/A/F) (where X can be any amino acid).<ref name="Alberts B, Johnson A, Lewis J-2002" />

There are also proteins that possess neither of these signals. Their transport may be based on a so-called "piggy-back" mechanism: such proteins associate with PTS1-possessing matrix proteins and are translocated into the peroxisomal matrix together with them.<ref>{{cite journal | vauthors = Saryi NA, Hutchinson JD, Al-Hejjaj MY, Sedelnikova S, Baker P, Hettema EH | title = Pnc1 piggy-back import into peroxisomes relies on Gpd1 homodimerisation | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 42579 | date = February 2017 | pmid = 28209961 | doi = 10.1038/srep42579 | pmc = 5314374 | bibcode = 2017NatSR...742579S }}</ref>

In the case of cytosolic proteins that are produced with the PTS1 C-terminal sequence, its path to the peroxisomal matrix is dependent upon binding to another cytosolic protein called [[PEX5|pex5]] (peroxin 5).<ref name="Baker A, Hogg T, Warriner S-2016">{{Cite journal |last=Baker A, Hogg T, Warriner S |date=2016 |title=Peroxisome protein import: a complex journey |journal=Biochemical Society Transactions |volume=44 |issue=3 |pages=783–789 |doi=10.1042/BST20160036 |pmid=27284042 |pmc=4900764 }}</ref> Once bound, pex5 interacts with a peroxisomal membrane protein [[PEX14|pex14]] to form a complex. When the pex5 protein with bound cargo interacts with the pex14 membrane protein, the complex induces the release of the targeted protein into the matrix. Upon releasing the cargo protein into the matrix, pex5 dissociation from pex14 occurs via [[ubiquitin]]ylation by a membrane complex comprising pex2, [[PEX12|pex12]], and [[PEX10|pex10]] followed by an ATP dependent removal involving the cytosolic protein complex [[PEX1|pex1]] and [[PEX6|pex6]].<ref>{{Cite journal |last=Gould S, Collins C |date=2002 |title=Peroxisomal-protein import: is it really that complex? |journal=Nature Rev. Mol. Cell Biol. |volume=3 |issue=5 |pages=382–389 |doi=10.1038/nrm807 |pmid=11988772 |s2cid=2522184 |doi-access=free }}</ref> The cycle for pex5 mediated import into the peroxisomal matrix is restored after the ATP dependent removal of [[ubiquitin]] and is free to bind with another protein containing a PTS1 sequence.<ref name="Baker A, Hogg T, Warriner S-2016" /> Proteins containing a PTS2 targeting sequence are mediated by a different cytosolic protein but are believed to follow a similar mechanism to that of those containing the PTS1 sequence.<ref name="Alberts B, Johnson A, Lewis J-2002" />