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'''Solute carrier family 25 member 46''' is a [[protein]] that in humans is encoded by the ''SLC25A46'' [[gene]]. This protein is a member of the [[Solute carrier family|SLC25 mitochondrial solute carrier]] [[Protein family|family]]. It is a [[transmembrane protein]] located in the [[Mitochondrion#Outer membrane|mitochondrial outer membrane]] involved in [[lipid]] transfer from the [[endoplasmic reticulum]] (ER) to [[Mitochondrion|mitochondria]].<ref name=":1">{{Cite journal|last=Abrams|first=Alexander J.|last2=Hufnagel|first2=Robert B.|last3=Rebelo|first3=Adriana|last4=Zanna|first4=Claudia|last5=Patel|first5=Neville|last6=Gonzalez|first6=Michael A.|last7=Campeanu|first7=Ion J.|last8=Griffin|first8=Laurie B.|last9=Groenewald|first9=Saskia|date=2015-8|title=Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/26168012|journal=Nature Genetics|volume=47|issue=8|pages=926–932|doi=10.1038/ng.3354|issn=1546-1718|pmc=PMC4520737|pmid=26168012}}</ref><ref name=":2">{{Cite journal|last=Janer|first=Alexandre|last2=Prudent|first2=Julien|last3=Paupe|first3=Vincent|last4=Fahiminiya|first4=Somayyeh|last5=Majewski|first5=Jacek|last6=Sgarioto|first6=Nicolas|last7=Des Rosiers|first7=Christine|last8=Forest|first8=Anik|last9=Lin|first9=Zhen-Yuan|date=09 2016|title=SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/27390132|journal=EMBO molecular medicine|volume=8|issue=9|pages=1019–1038|doi=10.15252/emmm.201506159|issn=1757-4684|pmc=PMC5009808|pmid=27390132}}</ref> [[Mutation|Mutations]] in this gene result in [[Optic neuropathy|neuropathy and optic atrophy]].<ref name="entrez">{{cite web|url=http://www.ncbi.nlm.nih.gov/gene/91137|title=Entrez Gene: Solute carrier family 25 member 46|accessdate=2018-08-17}}{{PD-notice}}</ref>
'''Solute carrier family 25 member 46''' is a [[protein]] that in humans is encoded by the ''SLC25A46'' [[gene]]. This protein is a member of the [[Solute carrier family|SLC25 mitochondrial solute carrier]] [[Protein family|family]]. It is a [[transmembrane protein]] located in the [[Mitochondrion#Outer membrane|mitochondrial outer membrane]] involved in [[lipid]] transfer from the [[endoplasmic reticulum]] (ER) to [[Mitochondrion|mitochondria]].<ref name=":1">{{cite journal | vauthors = Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schüle R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince J, Fontanesi F, Barrientos A, Németh AH, Carelli V, Huang T, Zuchner S, Dallman JE | title = Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder | journal = Nature Genetics | volume = 47 | issue = 8 | pages = 926–32 | date = August 2015 | pmid = 26168012 | pmc = 4520737 | doi = 10.1038/ng.3354 }}</ref><ref name=":2">{{cite journal | vauthors = Janer A, Prudent J, Paupe V, Fahiminiya S, Majewski J, Sgarioto N, Des Rosiers C, Forest A, Lin ZY, Gingras AC, Mitchell G, McBride HM, Shoubridge EA | title = SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome | journal = EMBO Molecular Medicine | volume = 8 | issue = 9 | pages = 1019–38 | date = September 2016 | pmid = 27390132 | pmc = 5009808 | doi = 10.15252/emmm.201506159 }}</ref> [[Mutation|Mutations]] in this gene result in [[Optic neuropathy|neuropathy and optic atrophy]].<ref name="entrez">{{cite web|url=http://www.ncbi.nlm.nih.gov/gene/91137|title=Entrez Gene: Solute carrier family 25 member 46|access-date=2018-08-17}}{{PD-notice}}</ref>


== Structure ==
== Structure ==
The ''SLC25A46'' gene is located on the q arm of [[chromosome 5]] in position 22.1 and spans 27,039 base pairs.<ref name="entrez" /> The gene produces a 46.2 kDa protein composed of 418 [[amino acids]].<ref name="COPaKB">{{cite journal|vauthors=Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P|date=Oct 2013|title=Integration of cardiac proteome biology and medicine by a specialized knowledgebase|journal=Circulation Research|volume=113|issue=9|pages=1043–53|doi=10.1161/CIRCRESAHA.113.301151|pmc=4076475|pmid=23965338}}</ref><ref name="url_COPaKB">{{cite web|url=https://amino.heartproteome.org/web/protein/Q8N5M1|title=SLC25A46 - Solute carrier family 25 member 46|work=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)}}</ref> This gene has 8 [[Exon|exons]] and encodes a [[Integral membrane protein#Integral polytopic protein|multi-pass]] [[integral membrane protein]] [[Protein subcellular localization prediction|localized]] to the mitochondrial outer membrane.<ref>Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {610826}: {09/19/2017}: . World Wide Web URL: https://omim.org/</ref><ref name=":0" /><ref name=":3" />
The ''SLC25A46'' gene is located on the q arm of [[chromosome 5]] in position 22.1 and spans 27,039 base pairs.<ref name="entrez" /> The gene produces a 46.2 kDa protein composed of 418 [[amino acids]].<ref name="COPaKB">{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web|url=https://amino.heartproteome.org/web/protein/Q8N5M1|title=SLC25A46 - Solute carrier family 25 member 46|work=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)}}</ref> This gene has 8 [[Exon|exons]] and encodes a [[Integral membrane protein#Integral polytopic protein|multi-pass]] [[integral membrane protein]] [[Protein subcellular localization prediction|localized]] to the mitochondrial outer membrane.<ref>{{OMIM|610826|solute carrier family 25, member 46; SLC25A46}}</ref><ref name=":0" /><ref name=":3" />


== Function ==
== Function ==
The encoded protein is an orphan transporter involved in lipid transfer from the endoplasmic reticulum to mitochondria.<ref>{{Cite journal|last=Palmieri|first=Ferdinando|date=2013-04|title=The mitochondrial transporter family SLC25: Identification, properties and physiopathology|url=http://linkinghub.elsevier.com/retrieve/pii/S0098299712000519|journal=Molecular Aspects of Medicine|volume=34|issue=2-3|pages=465–484|doi=10.1016/j.mam.2012.05.005|issn=0098-2997}}</ref><ref name=":2" /> It promotes [[mitochondrial fission]] and prevents the formation of hyperfilamentous mitochondria. This protein forms a [[Protein complex|complex]] with mitofilin ([[IMMT]]) on the inner mitochondrial membrane, independent of [[MFN2]].<ref name=":1" />
The encoded protein is an orphan transporter involved in lipid transfer from the endoplasmic reticulum to mitochondria.<ref>{{cite journal | vauthors = Palmieri F | title = The mitochondrial transporter family SLC25: identification, properties and physiopathology | journal = Molecular Aspects of Medicine | volume = 34 | issue = 2-3 | pages = 465–84 | date = 2013-04 | pmid = 23266187 | doi = 10.1016/j.mam.2012.05.005 | url = http://linkinghub.elsevier.com/retrieve/pii/S0098299712000519 }}</ref><ref name=":2" /> It promotes [[mitochondrial fission]] and prevents the formation of hyperfilamentous mitochondria. This protein forms a [[Protein complex|complex]] with mitofilin ([[IMMT]]) on the inner mitochondrial membrane, independent of [[MFN2]].<ref name=":1" />


== Clinical Significance ==
== Clinical Significance ==
Mutations in the ''SLC25A46'' gene, inherited in an [[Genetic disorder#Autosomal recessive|autosomal recessive]] manner, cause type 6B [[hereditary motor and sensory neuropathy]]. Symptoms include early-onset optic atrophy, progressive visual loss, and [[Peripheral neuropathy|peripheral sensorimotor neuropathy]] manifesting as [[Axon|axonal]] [[Charcot-Marie-Tooth disease]], with variable age at onset and severity.<ref name=":0">{{Cite web|url=https://www.uniprot.org/uniprot/Q96AG3|title=SLC25A46 - Solute carrier family 25 member 46 - Homo sapiens (Human) - SLC25A46 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-16}}{{CC-notice|cc=by4}}</ref><ref name=":3">{{cite journal|vauthors=|date=January 2017|title=UniProt: the universal protein knowledgebase|url=https://doi.org/10.1093/nar/gkw1099|journal=Nucleic Acids Research|volume=45|issue=D1|pages=D158-D169|doi=10.1093/nar/gkw1099|pmc=5210571|pmid=27899622}}</ref>
Mutations in the ''SLC25A46'' gene, inherited in an [[Genetic disorder#Autosomal recessive|autosomal recessive]] manner, cause type 6B [[hereditary motor and sensory neuropathy]]. Symptoms include early-onset optic atrophy, progressive visual loss, and [[Peripheral neuropathy|peripheral sensorimotor neuropathy]] manifesting as [[Axon|axonal]] [[Charcot-Marie-Tooth disease]], with variable age at onset and severity.<ref name=":0">{{Cite web|url=https://www.uniprot.org/uniprot/Q96AG3|title=SLC25A46 - Solute carrier family 25 member 46 - Homo sapiens (Human) - SLC25A46 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-16}}{{CC-notice|cc=by4}}</ref><ref name=":3">{{cite journal | vauthors = | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158-D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 | url = https://doi.org/10.1093/nar/gkw1099 }}</ref>


[[Gene expression|Overexpression]] of this protein causes mitochondrial fragmentation while [[Gene knockdown|knockdown]] of this protein causes [[Mitochondrial fusion|mitochondrial hyperfusion]] and hyperfilamentous mitochondria due to decreased mitochondrial fission.<ref name=":1" /> Loss of this gene also has many other effects: premature [[cellular senescence]], impaired [[cellular respiration]], destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortened [[Crista|cristae]], altered ER [[Morphology (biology)|morphology]], impaired [[cell migration]], and changes in mitochondrial [[phospholipid]] composition.<ref name=":2" />
[[Gene expression|Overexpression]] of this protein causes mitochondrial fragmentation while [[Gene knockdown|knockdown]] of this protein causes [[Mitochondrial fusion|mitochondrial hyperfusion]] and hyperfilamentous mitochondria due to decreased mitochondrial fission.<ref name=":1" /> Loss of this gene also has many other effects: premature [[cellular senescence]], impaired [[cellular respiration]], destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortened [[Crista|cristae]], altered ER [[Morphology (biology)|morphology]], impaired [[cell migration]], and changes in mitochondrial [[phospholipid]] composition.<ref name=":2" />
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== References ==
== References ==

{{reflist}}
{{reflist}}


== Further reading ==
== Further reading ==

{{refbegin|2}}
{{refbegin|2}}
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* {{cite journal | vauthors = Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ | title = Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression | journal = PloS One | volume = 5 | issue = 9 | pages = e12862 | date = September 2010 | pmid = 20877624 | pmc = 2943476 | doi = 10.1371/journal.pone.0012862 }}
*{{cite journal|vauthors=Vasan RS, Glazer NL, Felix JF, Lieb W, Wild PS, Felix SB, Watzinger N, Larson MG, Smith NL, Dehghan A, Grosshennig A, Schillert A, Teumer A, Schmidt R, Kathiresan S, Lumley T, Aulchenko YS, König IR, Zeller T, Homuth G, Struchalin M, Aragam J, Bis JC, Rivadeneira F, Erdmann J, Schnabel RB, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Levy D, Haritunians T, Deckers JW, Stritzke J, Lackner KJ, Völker U, Ingelsson E, Kullo I, Haerting J, O'Donnell CJ, Heckbert SR, Stricker BH, Ziegler A, Reffelmann T, Redfield MM, Werdan K, Mitchell GF, Rice K, Arnett DK, Hofman A, Gottdiener JS, Uitterlinden AG, Meitinger T, Blettner M, Friedrich N, Wang TJ, Psaty BM, van Duijn CM, Wichmann HE, Munzel TF, Kroemer HK, Benjamin EJ, Rotter JI, Witteman JC, Schunkert H, Schmidt H, Völzke H, Blankenberg S|date=July 2009|title=Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data|url=|journal=JAMA|volume=302|issue=2|pages=168–78|doi=10.1001/jama.2009.978-a|pmc=2975567|pmid=19584346}}
⚫
* {{cite journal | vauthors = Palmieri F | title = The mitochondrial transporter family SLC25: identification, properties and physiopathology | journal = Molecular Aspects of Medicine | volume = 34 | issue = 2-3 | pages = 465–84 | date = 2013 | pmid = 23266187 | doi = 10.1016/j.mam.2012.05.005 }}
⚫
*{{cite journal|vauthors=Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ|date=September 2010|title=Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression|url=|journal=PLoS ONE|volume=5|issue=9|pages=e12862|doi=10.1371/journal.pone.0012862|pmc=2943476|pmid=20877624}}
⚫
* {{cite journal | vauthors = Parry HM, Donnelly LA, Van Zuydam N, Doney AS, Elder DH, Morris AD, Struthers AD, Palmer CN, Lang CC | title = Genetic variants predicting left ventricular hypertrophy in a diabetic population: a Go-DARTS study including meta-analysis | journal = Cardiovascular Diabetology | volume = 12 | issue = | pages = 109 | date = July 2013 | pmid = 23879873 | pmc = 3729417 | doi = 10.1186/1475-2840-12-109 }}
⚫
*{{cite journal|vauthors=Palmieri F|date=2013|title=The mitochondrial transporter family SLC25: identification, properties and physiopathology|url=|journal=Mol. Aspects Med.|volume=34|issue=2-3|pages=465–84|doi=10.1016/j.mam.2012.05.005|pmid=23266187}}
⚫
* {{cite journal | vauthors = Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schüle R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince J, Fontanesi F, Barrientos A, Németh AH, Carelli V, Huang T, Zuchner S, Dallman JE | title = Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder | journal = Nature Genetics | volume = 47 | issue = 8 | pages = 926–32 | date = August 2015 | pmid = 26168012 | pmc = 4520737 | doi = 10.1038/ng.3354 }}
⚫
*{{cite journal|vauthors=Parry HM, Donnelly LA, Van Zuydam N, Doney AS, Elder DH, Morris AD, Struthers AD, Palmer CN, Lang CC|date=July 2013|title=Genetic variants predicting left ventricular hypertrophy in a diabetic population: a Go-DARTS study including meta-analysis|url=|journal=Cardiovasc Diabetol|volume=12|issue=|pages=109|doi=10.1186/1475-2840-12-109|pmc=3729417|pmid=23879873}}
* {{cite journal | vauthors = Gao J, Ma Y, Sheng Y, Zuo X, Wang W, Zheng X, Tang H, Tang X, Zhou F, Yang S, Zhang X, Sun L | title = Association analysis of allergic sensitization susceptibility loci with atopic dermatitis in Chinese population | journal = Journal of Dermatological Science | volume = 80 | issue = 3 | pages = 217–20 | date = December 2015 | pmid = 26464032 | doi = 10.1016/j.jdermsci.2015.09.009 }}
⚫
*{{cite journal|vauthors=Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schüle R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince J, Fontanesi F, Barrientos A, Németh AH, Carelli V, Huang T, Zuchner S, Dallman JE|date=August 2015|title=Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder|url=|journal=Nat. Genet.|volume=47|issue=8|pages=926–32|doi=10.1038/ng.3354|pmc=4520737|pmid=26168012}}
*{{cite journal|vauthors=Gao J, Ma Y, Sheng Y, Zuo X, Wang W, Zheng X, Tang H, Tang X, Zhou F, Yang S, Zhang X, Sun L|date=December 2015|title=Association analysis of allergic sensitization susceptibility loci with atopic dermatitis in Chinese population|url=|journal=J. Dermatol. Sci.|volume=80|issue=3|pages=217–20|doi=10.1016/j.jdermsci.2015.09.009|pmid=26464032}}
* {{cite journal | vauthors = Janer A, Prudent J, Paupe V, Fahiminiya S, Majewski J, Sgarioto N, Des Rosiers C, Forest A, Lin ZY, Gingras AC, Mitchell G, McBride HM, Shoubridge EA | title = SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome | journal = EMBO Molecular Medicine | volume = 8 | issue = 9 | pages = 1019–38 | date = September 2016 | pmid = 27390132 | pmc = 5009808 | doi = 10.15252/emmm.201506159 }}
*{{cite journal|vauthors=Janer A, Prudent J, Paupe V, Fahiminiya S, Majewski J, Sgarioto N, Des Rosiers C, Forest A, Lin ZY, Gingras AC, Mitchell G, McBride HM, Shoubridge EA|date=September 2016|title=SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome|url=|journal=EMBO Mol Med|volume=8|issue=9|pages=1019–38|doi=10.15252/emmm.201506159|pmc=5009808|pmid=27390132}}
* {{cite journal | vauthors = Wan J, Steffen J, Yourshaw M, Mamsa H, Andersen E, Rudnik-Schöneborn S, Pope K, Howell KB, McLean CA, Kornberg AJ, Joseph J, Lockhart PJ, Zerres K, Ryan MM, Nelson SF, Koehler CM, Jen JC | title = Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia | journal = Brain | volume = 139 | issue = 11 | pages = 2877–2890 | date = November 2016 | pmid = 27543974 | pmc = 5840878 | doi = 10.1093/brain/aww212 }}
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* {{cite journal | vauthors = Steffen J, Vashisht AA, Wan J, Jen JC, Claypool SM, Wohlschlegel JA, Koehler CM | title = Rapid degradation of mutant SLC25A46 by the ubiquitin-proteasome system results in MFN1/2-mediated hyperfusion of mitochondria | journal = Molecular Biology of the Cell | volume = 28 | issue = 5 | pages = 600–612 | date = March 2017 | pmid = 28057766 | pmc = 5328619 | doi = 10.1091/mbc.E16-07-0545 }}
*{{cite journal|vauthors=Wan J, Steffen J, Yourshaw M, Mamsa H, Andersen E, Rudnik-Schöneborn S, Pope K, Howell KB, McLean CA, Kornberg AJ, Joseph J, Lockhart PJ, Zerres K, Ryan MM, Nelson SF, Koehler CM, Jen JC|date=November 2016|title=Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia|url=|journal=Brain|volume=139|issue=11|pages=2877–2890|doi=10.1093/brain/aww212|pmc=5840878|pmid=27543974}}
⚫
*{{cite journal|vauthors=Steffen J, Vashisht AA, Wan J, Jen JC, Claypool SM, Wohlschlegel JA, Koehler CM|date=March 2017|title=Rapid degradation of mutant SLC25A46 by the ubiquitin-proteasome system results in MFN1/2-mediated hyperfusion of mitochondria|url=|journal=Mol. Biol. Cell|volume=28|issue=5|pages=600–612|doi=10.1091/mbc.E16-07-0545|pmc=5328619|pmid=28057766}}


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Revision as of 07:04, 18 August 2018

Solute carrier family 25 member 46 is a protein that in humans is encoded by the SLC25A46 gene. This protein is a member of the SLC25 mitochondrial solute carrier family. It is a transmembrane protein located in the mitochondrial outer membrane involved in lipid transfer from the endoplasmic reticulum (ER) to mitochondria.[1][2] Mutations in this gene result in neuropathy and optic atrophy.[3]

Structure

The SLC25A46 gene is located on the q arm of chromosome 5 in position 22.1 and spans 27,039 base pairs.[3] The gene produces a 46.2 kDa protein composed of 418 amino acids.[4][5] This gene has 8 exons and encodes a multi-pass integral membrane protein localized to the mitochondrial outer membrane.[6][7][8]

Function

The encoded protein is an orphan transporter involved in lipid transfer from the endoplasmic reticulum to mitochondria.[9][2] It promotes mitochondrial fission and prevents the formation of hyperfilamentous mitochondria. This protein forms a complex with mitofilin (IMMT) on the inner mitochondrial membrane, independent of MFN2.[1]

Clinical Significance

Mutations in the SLC25A46 gene, inherited in an autosomal recessive manner, cause type 6B hereditary motor and sensory neuropathy. Symptoms include early-onset optic atrophy, progressive visual loss, and peripheral sensorimotor neuropathy manifesting as axonal Charcot-Marie-Tooth disease, with variable age at onset and severity.[7][8]

Overexpression of this protein causes mitochondrial fragmentation while knockdown of this protein causes mitochondrial hyperfusion and hyperfilamentous mitochondria due to decreased mitochondrial fission.[1] Loss of this gene also has many other effects: premature cellular senescence, impaired cellular respiration, destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortened cristae, altered ER morphology, impaired cell migration, and changes in mitochondrial phospholipid composition.[2]

Interactions

This protein interacts with IMMT, a component of the MICOS complex, along with other components of this complex and components of an ER membrane protein complex involved in transferring lipids to mitochondria.[7][8][2] Additionally, this protein interacts with SLC7A8, SLC10A1, SLC10A6, FHL3, FUNDC1, linc01142, LEPROTL1, ODF4, VMA21, MFSD14B, PQLC1, HSD17B11, REEP2, REEP4, and TOMM22.[10] This protein possibly interacts with OPA1 and MFN2.[2]

References

  1. ^ a b c Abrams AJ, Hufnagel RB, Rebelo A, Zanna C, Patel N, Gonzalez MA, Campeanu IJ, Griffin LB, Groenewald S, Strickland AV, Tao F, Speziani F, Abreu L, Schüle R, Caporali L, La Morgia C, Maresca A, Liguori R, Lodi R, Ahmed ZM, Sund KL, Wang X, Krueger LA, Peng Y, Prada CE, Prows CA, Schorry EK, Antonellis A, Zimmerman HH, Abdul-Rahman OA, Yang Y, Downes SM, Prince J, Fontanesi F, Barrientos A, Németh AH, Carelli V, Huang T, Zuchner S, Dallman JE (August 2015). "Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder". Nature Genetics. 47 (8): 926–32. doi:10.1038/ng.3354. PMC 4520737. PMID 26168012.
  2. ^ a b c d e Janer A, Prudent J, Paupe V, Fahiminiya S, Majewski J, Sgarioto N, Des Rosiers C, Forest A, Lin ZY, Gingras AC, Mitchell G, McBride HM, Shoubridge EA (September 2016). "SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome". EMBO Molecular Medicine. 8 (9): 1019–38. doi:10.15252/emmm.201506159. PMC 5009808. PMID 27390132.
  3. ^ a b "Entrez Gene: Solute carrier family 25 member 46". Retrieved 2018-08-17.Public Domain This article incorporates text from this source, which is in the public domain.
  4. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  5. ^ "SLC25A46 - Solute carrier family 25 member 46". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  6. ^ Online Mendelian Inheritance in Man (OMIM): solute carrier family 25, member 46; SLC25A46 - 610826
  7. ^ a b c "SLC25A46 - Solute carrier family 25 member 46 - Homo sapiens (Human) - SLC25A46 gene & protein". www.uniprot.org. Retrieved 2018-08-16. This article incorporates text available under the CC BY 4.0 license.
  8. ^ a b c "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  9. ^ Palmieri F (2013-04). "The mitochondrial transporter family SLC25: identification, properties and physiopathology". Molecular Aspects of Medicine. 34 (2–3): 465–84. doi:10.1016/j.mam.2012.05.005. PMID 23266187. {{cite journal}}: Check date values in: |date= (help)
  10. ^ IntAct. "https://www.ebi.ac.uk/intact/interactions?conversationContext=1". www.ebi.ac.uk. Retrieved 2018-08-18. {{cite web}}: External link in |title= (help)

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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