Editing Uniporter

{{Redirect|Uniport|the university|Uniport (Nigeria)}}
{{Multiple issues|
{{More footnotes needed|date=May 2015}}
{{page numbers needed|date=May 2015}}
}}
[[Image:Porters.PNG|right|thumb|250px|Comparison of transport proteins]]

'''Uniporters,''' also known as '''solute carriers''' or '''facilitated transporters''', are a type of [[membrane transport protein]] that passively transports solutes (small molecules, ions, or other substances) across a cell membrane.<ref name="Zhang XC">{{cite journal |vauthors=Zhang XC, Han L |title=Uniporter substrate binding and transport: reformulating mechanistic questions |journal=Biophys Rep |volume=2 |issue=2–4 |pages=45–54 |date=2016 |pmid=28018963 |pmc=5138270 |doi=10.1007/s41048-016-0030-7 }}</ref>  It uses [[facilitated diffusion]] for the movement of solutes down their concentration gradient from an area of high concentration to an area of low concentration.<ref name="Alberts">{{cite book |first=Bruce |last=Alberts |title=Essential cell biology : an introduction to the molecular biology of the cell |publisher=Garland |oclc=36847771 |date=1998 |isbn=0-8153-2045-0 }}</ref> Unlike [[active transport]], it does not require energy in the form of [[Adenosine triphosphate|ATP]] to function. Uniporters are specialized to carry one specific ion or molecule and can be categorized as either channels or carriers.<ref>{{cite journal |vauthors=Wolfersberger MG |title=Uniporters, symporters and antiporters |journal=J Exp Biol |volume=196 |issue= |pages=5–6 |date=November 1994 |pmid=7823043 |doi=10.1242/jeb.196.1.5 }}</ref> Facilitated diffusion may occur through three mechanisms: uniport, symport, or antiport. The difference between each mechanism depends on the direction of transport, in which uniport is the only transport not coupled to the transport of another solute.<ref>{{cite book |vauthors=Pratt CA, Voet D, Voet JG |title=Fundamentals of biochemistry |publisher=Wiley |oclc=48137160 |date=2002 |isbn=0-471-41759-9 |pages=264–6 }}</ref>

Uniporter carrier proteins work by binding to one [[molecule]] or [[Substrate (biochemistry)|substrate]] at a time. Uniporter channels open in response to a stimulus and allow the free flow of specific molecules.<ref name="Alberts" />

There are several ways in which the opening of uniporter channels may be regulated:

# [[Voltage]] – Regulated by the difference in voltage across the membrane
# [[Stress (physics)|Stress]] – Regulated by physical [[pressure]] on the transporter (as in the [[cochlea]] of the [[ear]])
# [[Ligand]] – Regulated by the binding of a ligand to either the intracellular or extracellular side of the [[Cell (biology)|cell]]
Uniporters are found in [[Mitochondrion|mitochondria]], [[Cell membrane|plasma membranes]] and [[neuron]]s.The uniporter in the mitochondria is responsible for [[calcium]] uptake.<ref name="Zhang XC" /> The calcium channels are used for [[cell signaling]] and triggering [[apoptosis]]. The calcium uniporter transports calcium across the inner mitochondrial membrane and is activated when calcium rises above a certain concentration.<ref>{{Cite journal |last=Hoppe |first=U. |date=2010 |title=Mitochondrial Calcium Channels |journal=FEBS Letters |volume=584 |issue=10 |pages=1975–81 |doi=10.1016/j.febslet.2010.04.017 |pmid=20388514 |s2cid=33664763|doi-access=free |bibcode=2010FEBSL.584.1975H }}</ref> The [[CD98|amino acid transporters]] function in transporting neutral [[amino acid]]s for [[neurotransmitter]] production in brain cells.<ref name="Häfliger P" /> [[Voltage-gated potassium channel]]s are also uniporters found in neurons and are essential for [[action potential]]s.<ref>{{cite journal |vauthors=Kim DM, Nimigean CM |title=Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating |journal=Cold Spring Harb Perspect Biol |volume=8 |issue=5 |pages= a029231|date=May 2016 |pmid=27141052 |pmc=4852806 |doi=10.1101/cshperspect.a029231 }}</ref> This channel is activated by a voltage gradient created by [[Na+/K+-ATPase|sodium-potassium pumps]]. When the membrane reaches a certain voltage, the channels open, which [[Depolarization|depolarizes]] the membrane, leading to an [[action potential]] being sent down the membrane.<ref>{{Cite book |last=OpenStax College |title=Chapter 12.4 The Action Potential |publisher=OpenStax College |year=2013 |isbn=978-1938168130 |pages=523–531}}</ref> [[Glucose transporter]]s are found in the plasma membrane and play a role in transporting [[glucose]]. They help to bring glucose from the blood or extracellular space into cells usually to be utilized for metabolic processes in generating energy.<ref name="Olson AL" />

Uniporters are essential for certain physiological processes in cells, such as nutrient uptake, waste removal, and maintenance of ionic balance.

== Discovery ==
[[File:Scheme facilitated diffusion in cell membrane-en.svg|thumb|Facilitated diffusion using transport proteins]]
Early research in the 19th and 20th centuries on [[osmosis]] and [[diffusion]] provided the foundation for understanding the [[Passive transport|passive movement]] of molecules across cell membranes.<ref>{{cite book |vauthors=Cooper GM |chapter=12.2 Transport of Small Molecules |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK9847/ |id=NBK9847 |title=The Cell: A Molecular Approach |edition=2nd |publisher=Sinauer Associates |location=Sunderland MA |date=2000 |isbn=0-87893-106-6 |pages= |url=https://www.ncbi.nlm.nih.gov/books/NBK9839/}}</ref>

In 1855, the physiologist [[Adolf Eugen Fick|Adolf Fick]] was the first to define osmosis and simple diffusion as the tendency for [[Solution (chemistry)|solutes]] to move from a region of higher concentration to a lower concentration, also very well-known as [[Fick's laws of diffusion|Fick's Laws of Diffusion]].<ref name="Stillwell W">{{cite book |vauthors=Stillwell W |chapter=Membrane Transport |chapter-url= |editor= |title=An Introduction to Biological Membranes |publisher= |location= |date=2016 |isbn=978-0-444-63772-7 |doi=10.1016/B978-0-444-63772-7.00019-1 |pages=423–51 |pmc=7182109}}</ref> Through the work of [[Charles Overton]] in the 1890s, the concept that the [[biological membrane]] is [[Semipermeable membrane|semipermeable]] became important to understanding the regulation of substances in and out of the cells.<ref name="Stillwell W" /> The discovery of [[facilitated diffusion]] by Wittenberg and Scholander suggested that [[protein]]s in the cell membrane aid in the transport of molecules.<ref>{{cite journal |vauthors=Rubinow SI, Dembo M |title=The facilitated diffusion of oxygen by hemoglobin and myoglobin |journal=Biophys J |volume=18 |issue=1 |pages=29–42 |date=April 1977 |pmid=856316 |pmc=1473276 |doi=10.1016/S0006-3495(77)85594-X |bibcode=1977BpJ....18...29R }}</ref> In the 1960s - 1970s, studies on the transport of [[glucose]] and other nutrients highlighted the [[Specificity (biochemistry)|specificity]] and [[Selectivity (biochemistry)|selectivity]] of [[membrane transport protein]]s.<ref>{{cite journal |vauthors=Wright EM, Loo DD, Hirayama BA |title=Biology of human sodium glucose transporters |journal=Physiol Rev |volume=91 |issue=2 |pages=733–94 |date=April 2011 |pmid=21527736 |doi=10.1152/physrev.00055.2009 }}</ref>

Technological advancements in biochemistry helped isolate and characterize these proteins from cell membranes. Genetic studies on [[bacteria]] and [[yeast]] identified genes responsible for encoding transporters. This led to the discovery of [[SLC2A10|glucose transporters]] (GLUT proteins), with [[GLUT1]] being the first to be characterized.<ref name="Thorens B">{{cite journal |vauthors=Thorens B, Mueckler M |title=Glucose transporters in the 21st Century |journal=Am J Physiol Endocrinol Metab |volume=298 |issue=2 |pages=E141–5 |date=February 2010 |pmid=20009031 |pmc=2822486 |doi=10.1152/ajpendo.00712.2009 }}</ref> Identification of gene families encoding various transporters, such as [[Solute carrier family|solute carrier (SLC) families]], also advanced knowledge on uniporters and its functions.<ref name="Thorens B" />

Newer research is focusing on techniques using [[Recombinant DNA|recombinant DNA technology]], [[electrophysiology]] and advanced imaging to understand uniporter functions. These experiments are designed to [[Cloning vector|clone]] and express transporter genes in host cells to further analyze the three-dimensional structure of uniporters, as well as directly observe the movement of ions through proteins in real-time.<ref name="Thorens B" /> The discovery of [[mutation]]s in uniporters has been linked to diseases such as [[GLUT1 deficiency syndrome]], [[cystic fibrosis]], [[Hartnup disease]], [[primary hyperoxaluria]] and [[hypokalemic periodic paralysis]].<ref>{{cite journal |vauthors=Shamseldin HE, Alasmari A, Salih MA, Samman MM, Mian SA, Alshidi T, Ibrahim N, Hashem M, Faqeih E, Al-Mohanna F, Alkuraya FS |title=A null mutation in MICU2 causes abnormal mitochondrial calcium homeostasis and a severe neurodevelopmental disorder |journal=Brain |volume=140 |issue=11 |pages=2806–13 |date=November 2017 |pmid=29053821 |doi=10.1093/brain/awx237 }}</ref>

== Types ==
=== Glucose transporter (GLUTs) ===

The glucose transporter (GLUTs) is a type of uniporter responsible for the [[facilitated diffusion]] of glucose molecules across cell membranes.<ref name="Olson AL">{{cite journal |vauthors=Olson AL, Pessin JE |title=Structure, function, and regulation of the mammalian facilitative glucose transporter gene family |journal=Annu Rev Nutr |volume=16 |issue= |pages=235–56 |date=1996 |pmid=8839927 |doi=10.1146/annurev.nu.16.070196.001315 }}</ref>[[Glucose]] is a vital energy source for most living cells, however, due to its large size, it cannot freely move through the cell membrane.<ref name="Navale AM">{{cite journal |vauthors=Navale AM, Paranjape AN |title=Glucose transporters: physiological and pathological roles |journal=Biophys Rev |volume=8 |issue=1 |pages=5–9 |date=March 2016 |pmid=28510148 |pmc=5425736 |doi=10.1007/s12551-015-0186-2 }}</ref> The glucose transporter is specialized in transporting glucose specifically across the membrane. The GLUT proteins have several types of [[Protein isoform|isoforms]], each distributed in different [[Tissue (biology)|tissues]] and exhibiting different [[Chemical kinetics|kinetic properties.]]<ref name="Navale AM" />
[[File:Glucose-6-phosphatase system.svg|thumb|Glucose transporter]]
GLUTs are [[integral membrane protein]]s composed of [[Alpha helix|12 α-helix membrane spanning regions]].<ref name="Navale AM" /> The GLUT proteins are encoded by the [[SLA2|SLC2 genes]] and categorized into three classes based on [[Protein primary structure|amino acid sequence]] similarity.<ref>{{cite journal |vauthors=Mueckler M, Thorens B |title=The SLC2 (GLUT) family of membrane transporters |journal=Mol Aspects Med |volume=34 |issue=2–3 |pages=121–38 |date=2013 |pmid=23506862 |pmc=4104978 |doi=10.1016/j.mam.2012.07.001 }}</ref> Humans have been found to express fourteen GLUT proteins. Class I GLUTs include [[GLUT1]], one of the most studied isoforms, and [[GLUT2]].<ref name="Navale AM" /> GLUT1 is found in various tissues like the [[red blood cell]]s, [[brain]], and [[Blood–brain barrier|blood-brain barrier]] and is responsible for basal [[glucose uptake]].<ref name="Navale AM" /> GLUT2 is predominantly found in the [[liver]], [[pancreas]], and [[small intestine]]s.<ref name="Navale AM" /> It plays an important role in insulin secretion from [[Beta cell|pancreatic beta cells]]. Class II includes the [[GLUT3]] and [[GLUT4]].<ref name="Navale AM" /> GLUT3, primarily found in the brain, [[neuron]]s and [[placenta]], has a high  [[Affinity electrophoresis|affinity]] for glucose in facilitating glucose uptake into neurons.<ref name="Navale AM" /> [[GLUT4]] plays a role in insulin-regulated glucose uptake and is mainly found in insulin-sensitive tissues such as muscle and [[adipose tissue]].<ref name="Navale AM" /> Class III includes [[GLUT5]], found in the [[small intestine]], [[kidney]], [[Testicle|testes]], and [[skeletal muscle]].<ref name="Navale AM" /> Unlike the other GLUTs, GLUT5 specifically transports [[fructose]] rather than glucose.<ref name="Navale AM" />

Glucose transporters allow glucose molecules to move down their concentration gradient from areas of high glucose concentration to areas of low concentration. This process often involves bringing glucose from the [[extracellular space]] or [[blood]] into the cell. The concentration gradient set up by glucose concentrations fuels the process without the need for ATP.<ref>{{cite journal |vauthors=Carruthers A |title=Facilitated diffusion of glucose |journal=Physiol Rev |volume=70 |issue=4 |pages=1135–76 |date=October 1990 |pmid=2217557 |doi=10.1152/physrev.1990.70.4.1135 }}</ref>

When glucose binds to the glucose transporter, the protein channels change shape and undergo a conformational change to transport the glucose across the membrane. Once the glucose unbinds, the protein returns to its original shape. The glucose transporter is essential for carrying out physiological processes that require high energy demands in the brain, muscles, and kidneys by providing an adequate amount of energy substrate for [[metabolism]]. [[Diabetes]], an example of a condition that involves glucose metabolism, highlights the importance of the regulation of glucose uptake in disease management.<ref>{{cite journal |vauthors=Jiang S, Young JL, Wang K, Qian Y, Cai L |title=Diabetic&#x2011;induced alterations in hepatic glucose and lipid metabolism: The role of type 1 and type 2 diabetes mellitus (Review) |journal=Mol Med Rep |volume=22 |issue=2 |pages=603–611 |date=August 2020 |pmid=32468027 |pmc=7339764 |doi=10.3892/mmr.2020.11175 }}</ref>

=== Mitochondrial {{chem2|Ca(2+)}} uniporter (MCU) ===
The '''mitochondrial calcium uniporter''' (MCU) is a protein complex located in the inner mitochondrial matrix that functions to take up calcium ions (Ca2+) into the [[Mitochondrial matrix|matrix]] from the [[cytoplasm]].<ref name="De Stefani D">{{cite journal |vauthors=De Stefani D, Patron M, Rizzuto R |title=Structure and function of the mitochondrial calcium uniporter complex |journal=Biochim Biophys Acta |volume=1853 |issue=9 |pages=2006–11 |date=September 2015 |pmid=25896525 |pmc=4522341 |doi=10.1016/j.bbamcr.2015.04.008 }}</ref> The transport of calcium ions is specifically used in cellular function for regulating energy production in the mitochondria, cytosolic [[calcium signaling]], and [[cell death]]. The uniporter becomes activated when cytoplasmic levels of calcium rise above 1 uM.<ref name="De Stefani D" />

The [[Mitochondrial calcium uniporter|MCU complex]] comprises 4 parts: the port-forming subunits, regulatory subunits [[MICU1 (gene)|MICU1]] and MICU2, and an auxiliary subunit, EMRE.<ref name="D'Angelo D">{{cite journal |vauthors=D'Angelo D, Rizzuto R |title=The Mitochondrial Calcium Uniporter (MCU): Molecular Identity and Role in Human Diseases |journal=Biomolecules |volume=13 |issue=9 |date=August 2023 |page=1304 |pmid=37759703 |pmc=10526485 |doi=10.3390/biom13091304 |doi-access=free }}</ref> These subunits work together to regulate the uptake of calcium in the mitochondria. Specifically, the EMRE subunit functions for the transport of calcium, and the MICU subunit functions in tightly regulating the activity of MCU to prevent the overload of calcium concentrations in the cytoplasm.<ref name="D'Angelo D" /> Calcium is fundamental for signaling pathways in cells, as well as for cell death pathways.<ref name="D'Angelo D" /> The function of the mitochondrial uniporter is critical for maintaining cellular [[homeostasis]].

The MICU1 and MICU2 subunits are a [[Protein dimer|heterodimer]] connected by a [[Disulfide|disulfide bridge]].<ref name="De Stefani D" /> When there are high levels of cytoplasmic calcium, the MICU1-MICU2 heterodimer undergoes a [[conformational change]].<ref name="De Stefani D" /> The heterodimer subunits have cooperative activation, which means {{chem2|Ca(2+)}} binding to one MICU subunit in the heterodimer induces a conformational change on the other MICU subunits. The uptake of calcium is balanced by the [[sodium-calcium exchanger]].<ref name="D'Angelo D" />

=== Large neutral amino acid transporter (LAT1) ===
[[File:Protein SLC3A2 PDB 2dh2.png|thumb|SLC3 protein coding gene for LAT1]]
The '''L-type amino acid transporter (LAT1)''' is a uniporter that mediates the transport of [[Neutral amino acid transporter A|neutral amino acids]] like [[Tryptophan|L-tryptophan]], [[leucine]], [[histidine]], [[proline]], [[alanine]], etc.<ref name="Häfliger P">{{cite journal |vauthors=Häfliger P, Charles RP |title=The L-Type Amino Acid Transporter LAT1-An Emerging Target in Cancer |journal=Int J Mol Sci |volume=20 |issue=10 |date=May 2019 |page=2428 |pmid=31100853 |pmc=6566973 |doi=10.3390/ijms20102428 |doi-access=free }}</ref> [[CD98|LAT1]] favors the transport of amino acids with large branched or [[Amino acid|aromatic side chains]]. The amino acid transporter functions to move essential amino acids into the [[intestinal epithelium]], [[placenta]], and [[Blood–brain barrier|blood-brain barrier]] for cellular processes such as metabolism and cell signaling.<ref name="Bhutia YD">{{cite journal |vauthors=Bhutia YD, Mathew M, Sivaprakasam S, Ramachandran S, Ganapathy V |title=Unconventional Functions of Amino Acid Transporters: Role in Macropinocytosis (SLC38A5/SLC38A3) and Diet-Induced Obesity/Metabolic Syndrome (SLC6A19/SLC6A14/SLC6A6) |journal=Biomolecules |volume=12 |issue=2 |date=January 2022 |page=235 |pmid=35204736 |pmc=8961558 |doi=10.3390/biom12020235 |doi-access=free }}</ref> The transporter is of particular significance in the [[central nervous system]] as it provides the necessary amino acids for protein synthesis and [[Neurotransmitter|neurotransmitter production]] in brain cells.<ref name="Bhutia YD" /> [[Aromatic amino acid]]s like [[phenylalanine]] and [[tryptophan]] are precursors for neurotransmitters like [[dopamine]], [[serotonin]], and [[norepinephrine]].<ref name="Bhutia YD" />

LAT1 is a membrane protein of the [[SLC7A14|SLC7]] family of transporters and works in conjunction with the [[Solute carrier family|SLC3 family]] member [[4F2 cell-surface antigen heavy chain|4F2hc]] to form a [[Protein dimer|heterodimeric]] complex known as the 4F2hc complex.<ref name="Häfliger P" /> The heterodimer consists of a light chain and a heavy chain [[Covalent bond|covalently bonded]] by a [[disulfide bond]]. The light chain is the one that carries out transport, while the heavy chain is needed to stabilize the dimer.<ref name="Häfliger P" />

There is some controversy over whether LAT1 is an uniporter or an [[antiporter]]. The transporter has uniporter characteristics of transporting amino acids into cells in a unidirectional manner down the concentration gradient. However, recently it has been found that the transporter has antiporter characteristics of exchanging neutral amino acids for abundant intracellular amino acids.<ref>{{cite journal |vauthors=Singh N, Ecker GF |title=Insights into the Structure, Function, and Ligand Discovery of the Large Neutral Amino Acid Transporter 1, LAT1 |journal=Int J Mol Sci |volume=19 |issue=5 |date=April 2018 |page=1278 |pmid=29695141 |pmc=5983779 |doi=10.3390/ijms19051278 |doi-access=free }}</ref>  Over-expression of LAT1 has been found in human [[cancer]] and is associated with playing a role in cancer metabolism.<ref>{{cite journal |vauthors=Kanai Y |title=Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics |journal=Pharmacol Ther |volume=230 |issue= |pages=107964 |date=February 2022 |pmid=34390745 |doi=10.1016/j.pharmthera.2021.107964 }}</ref>

=== Equilibrative nucleoside transporters (ENTs) ===
The '''nucleoside transporters''', or '''equilibrative nucleoside transporters''', are uniporters that transport [[nucleoside]]s, [[nucleobase]]s, and [[Pharmacology|therapeutic drugs]] across the cell membrane.<ref name="Boswell">{{cite journal |vauthors=Boswell-Casteel RC, Hays FA |title=Equilibrative nucleoside transporters-A review |journal=Nucleosides Nucleotides Nucleic Acids |volume=36 |issue=1 |pages=7–30 |date=January 2017 |pmid=27759477 |pmc=5728162 |doi=10.1080/15257770.2016.1210805 }}</ref> Nucleosides serve as building blocks for [[Nucleic acid|nucleic acid synthesis]] and are key components for energy metabolism in creating [[Adenosine triphosphate|ATP]]/ [[Guanosine triphosphate|GTP]].<ref name="Hollenstein M">{{cite journal |vauthors=Hollenstein M |title=Nucleoside triphosphates--building blocks for the modification of nucleic acids |journal=Molecules |volume=17 |issue=11 |pages=13569–91 |date=November 2012 |pmid=23154273 |pmc=6268876 |doi=10.3390/molecules171113569 |doi-access=free }}</ref> They also act as ligands for [[Receptors, amino acid|purinergic receptors]] such as [[adenosine]] and [[inosine]]. ENTs allow the transport of nucleosides down their concentration gradient. They also have the ability to deliver nucleoside analogs to intracellular targets for the treatment of [[Neoplasm|tumors]] and viral infections.<ref name="Hollenstein M" />

ENTs are part of the [[Major facilitator superfamily|Major Facilitator Superfamily (MFS)]] and are suggested to transport nucleosides using a clamp-and-switch model.<ref name="Hollenstein M" /> In this model, the substrate first binds to the transporter, which leads to a conformational change that forms an occluded state (clamp). Then, the transporter switches to face the other side of the membrane and releases the bound substrate (switching).<ref name="Hollenstein M" />

ENTs have been found in [[protozoa]] and mammals. In humans, they have been discovered as ENT3 (hENT1-3) and [[ENT4]] (hENT4) transporters.<ref name="Boswell" /> ENTs are expressed across all tissue types, but certain ENT proteins have been found to be more abundant in specific tissues. hENT1 is found mostly in the [[adrenal gland]]s, [[ovary]], [[stomach]] and [[small intestine]]s.<ref name="Boswell" /> hENT2 is expressed mostly in neurological tissues and small parts of the [[skin]], placenta, [[Bladder|urinary bladder]], [[Cardiac muscle|heart muscle]] and [[gallbladder]].<ref name="Boswell" /> hENT3 is expressed highly in the [[cerebral cortex]], [[Lateral ventricles|lateral ventricle]], [[ovary]] and [[adrenal gland]].<ref name="Boswell" /> hENT4 is more commonly known as the [[Plasma membrane monoamine transporter|plasma membrane monoamine transporter (PMAT)]], as it facilitates the movement of organic [[Ion|cations]] and biogenic [[amine]]s across the membrane.<ref name="Boswell" />

== Mechanism ==
[[File:Uniporter attivo.gif|thumb|Mechanism of uniport transport across cell membrane]]Uniporters work to transport molecules or ions by [[passive transport]] across a cell membrane down its [[Fick's laws of diffusion|concentration gradient.]]

Upon binding and recognition of a specific substrate molecule on one side of the uniporter membrane, a [[conformational change]] is triggered in the transporter protein.<ref name="Fan">{{cite journal |vauthors=Fan M, Zhang J, Tsai CW, Orlando BJ, Rodriguez M, Xu Y, Liao M, Tsai MF, Feng L |title=Structure and mechanism of the mitochondrial Ca<sup>2+</sup> uniporter holocomplex |journal=Nature |volume=582 |issue=7810 |pages=129–133 |date=June 2020 |pmid=32494073 |pmc=7544431 |doi=10.1038/s41586-020-2309-6 |bibcode=2020Natur.582..129F }}</ref> This causes the transporter protein to change its three-dimensional shape, which ensures the substrate molecule is captured within the transporter proteins structure. The conformational change leads to the translocation of the substrate across the membrane onto the other side.<ref name="Fan" /> On the other side of the membrane, the uniporter undergoes another conformational change in the release of the substrate molecule. The uniporter returns to its original conformation to bind another molecule for transport.<ref name="Fan" />

Unlike [[symporter]]s and [[antiporter]]s, uniporters transport one molecule/ion in a single direction based on the concentration gradient.<ref name="Majumder P">{{cite journal |vauthors=Majumder P, Mallela AK, Penmatsa A |title=Transporters through the looking glass. An insight into the mechanisms of ion-coupled transport and methods that help reveal them |journal=J Indian Inst Sci |volume=98 |issue=3 |pages=283–300 |date=September 2018 |pmid=30686879 |pmc=6345361 |doi=10.1007/s41745-018-0081-5 }}</ref> The entire process depends on the substrate's concentration difference across the membrane to be the driving force for the transport by uniporters.<ref name="Majumder P" /> Cellular energy in the form of [[ATP-binding motif|ATP]] is not required for this process.<ref name="Majumder P" />

== Physiological processes ==
Uniporters play an essential role in carrying out various cellular functions. Each uniporter is specialized to facilitate the transport of a specific molecule or ion across the cell membrane. Examples of a few of the physiological roles uniporters aid in include:<ref name="David R">{{cite journal |vauthors=David R, Byrt CS, Tyerman SD, Gilliham M, Wege S |title=Roles of membrane transporters: connecting the dots from sequence to phenotype |journal=Ann Bot |volume=124 |issue=2 |pages=201–8 |date=September 2019 |pmid=31162525 |pmc=6758574 |doi=10.1093/aob/mcz066 }}</ref>
# Nutrient Uptake: Uniporters facilitate the transport of essential [[nutrient]]s into the cell. Glucose transporters (GLUTs) are uniporters that uptake glucose for [[ATP synthase|energy production]].<ref name="David R" />
# Ion homeostasis: Uniporters facilitate in maintaining the balance of ions (i.e., {{chem2|link=Na+ channel|Na+}} {{chem2|link=Potassium channel|K+}}, {{chem2|link=Calcium channel|Ca(2+)}}, {{chem2|link=Chloride channel|Cl-}})  within cells <ref>{{cite journal |vauthors=Zhang R, Kang R, Klionsky DJ, Tang D |title=Ion Channels and Transporters in Autophagy |journal=Autophagy |volume=18 |issue=1 |pages=4–23 |date=January 2022 |pmid=33657975 |pmc=8865261 |doi=10.1080/15548627.2021.1885147 }}</ref>
# [[Metabolism]]: Uniporters are involved in the transport of essential ions, [[amino acid]]s and molecules required for the [[metabolic pathway]], [[Protein biosynthesis|protein synthesis]] and energy production<ref name="De Stefani D" />
# [[Cell signaling]]: Calcium uniporters help regulate intercellular calcium levels essential for [[signal transduction]]<ref name="Zhang XC" />
# Waste removal: Uniporters aid in removing [[metabolic waste]] products and toxins from cells
# [[Acid–base homeostasis|pH regulation]]: Transport of ions by uniporters also helps to maintain the overall [[acid-base balance]] within cells <ref>{{cite journal |vauthors=Seifter JL, Chang HY |title=Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments |journal=Physiology (Bethesda) |volume=32 |issue=5 |pages=367–379 |date=September 2017 |pmid=28814497 |doi=10.1152/physiol.00007.2017 }}</ref>

== Mutations ==
Mutations in genes encoding uniporters lead to dysfunctional transporter proteins being formed. This loss of function in uniporters causes disruption in cellular function which leads to various [[disease]]s and disorders.   
{| class="wikitable"
|+
!Gene with mutation
!Disease
!Result of disease
|-
|Mutations in the [[GLUT1|SLC2A1 gene]] which encode glucose transporters (GLUTs) <ref name="MedlinePlus">{{MedlinePlusEncyclopedia|001656|Noonan syndrome}}</ref>
|[[GLUT1 deficiency|GLUT1 Deficiency Syndrome]]<ref name="MedlinePlus" />
|Impaired glucose transport across the blood-brain barriers, and neurological symptoms such as seizures, development delay, and movement disorders <ref name="MedlinePlus-2">{{cite web |title=GLUT1 deficiency syndrome |work=Genetic Conditions |publisher=MedlinePlus |url=https://medlineplus.gov/genetics/condition/glut1-deficiency-syndrome/}}</ref>
|-
|Mutations in the [[Cystic fibrosis transmembrane conductance regulator|CFTR gene]] encoding [[ion channel]]s<ref name="MedlinePlus" />
|[[Cystic fibrosis|Cystic Fibrosis]]<ref name="MedlinePlus" />
|Problems with breathing and digestion due to thick mucus forming; affects multiple organs, primarily the lungs and digestive system <ref name="MedlinePlus-2" />
|-
|Mutation in [[KCNA3|KCNA1 gene]] encoding [[potassium channel]]s<ref name="MedlinePlus" />
|[[Hypokalemic periodic paralysis|Hypokalemic Periodic Paralysis]]<ref name="MedlinePlus" />
|Periodic muscle weakness; associated with low potassium levels due to altered transport activity <ref name="MedlinePlus-2" />
|-
|Mutations in the [[SLC6A19 (gene)|SLC6A19 gene]] encoding amino acid transporter <ref name="MedlinePlus" />
|[[Hartnup disease|Hartnup Disease]]<ref name="MedlinePlus" />
|Impaired absorption of certain amino acid in the intestines and kidneys <ref name="MedlinePlus-2" />
|-
|Mutations in the [[AGXT|AGXT gene]] encoding peroxisomal membrane transporter <ref name="MedlinePlus" />
|[[Primary hyperoxaluria|Primary Hyperoxaluria]]<ref name="MedlinePlus" />
|Metabolic disease; Leads to accumulation of oxalate in causing kidney stone and damage <ref name="MedlinePlus-2" />
|}

==See also==
* [[Antiporter]]
* [[Symporter]]

== References ==
{{reflist}}

{{Membrane transport}}

[[Category:Integral membrane proteins]]
[[Category:Transport phenomena]]