SLC25A46
SLC25A46 | |||
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Identifiers | |||
Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 5: 110.74 – 110.77 Mb | Chr 18: 31.69 – 31.74 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
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.[5][6] Mutations in this gene result in neuropathy and optic atrophy.[7]
Structure
The SLC25A46 gene is located on the q arm of
Function
The encoded protein is an orphan transporter involved in lipid transfer from the endoplasmic reticulum to mitochondria.[13][6] 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.[5]
Clinical Significance
Mutations in the SLC25A46 gene, inherited in an
Overexpression of this protein causes mitochondrial fragmentation while knockdown of this protein causes mitochondrial hyperfusion and hyperfilamentous mitochondria due to decreased mitochondrial fission.[5] 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.[6]
Interactions
This protein
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000164209 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024259 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 26168012.
- ^ PMID 27390132.
- ^ a b "Entrez Gene: Solute carrier family 25 member 46". Retrieved 2018-08-17. This article incorporates text from this source, which is in the public domain.
- PMID 23965338.
- ^ "SLC25A46 - Solute carrier family 25 member 46". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).[permanent dead link]
- ^ Online Mendelian Inheritance in Man (OMIM): solute carrier family 25, member 46; SLC25A46 - 610826
- ^ 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.
- ^ PMID 27899622.
- PMID 23266187.
- ^ "SLC25A46 binary interactions found for search term SLC25A46". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-18.
Further reading
- 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 (September 2010). "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression". PLOS ONE. 5 (9): e12862. PMID 20877624.
- Palmieri F (2013). "The mitochondrial transporter family SLC25: identification, properties and physiopathology". Molecular Aspects of Medicine. 34 (2–3): 465–84. PMID 23266187.
- Parry HM, Donnelly LA, Van Zuydam N, Doney AS, Elder DH, Morris AD, Struthers AD, Palmer CN, Lang CC (July 2013). "Genetic variants predicting left ventricular hypertrophy in a diabetic population: a Go-DARTS study including meta-analysis". Cardiovascular Diabetology. 12: 109. PMID 23879873.
- Gao J, Ma Y, Sheng Y, Zuo X, Wang W, Zheng X, Tang H, Tang X, Zhou F, Yang S, Zhang X, Sun L (December 2015). "Association analysis of allergic sensitization susceptibility loci with atopic dermatitis in Chinese population". Journal of Dermatological Science. 80 (3): 217–20. PMID 26464032.
- 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. PMID 27390132.
- 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 (November 2016). "Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia". Brain. 139 (11): 2877–2890. PMID 27543974.
- Steffen J, Vashisht AA, Wan J, Jen JC, Claypool SM, Wohlschlegel JA, Koehler CM (March 2017). "Rapid degradation of mutant SLC25A46 by the ubiquitin-proteasome system results in MFN1/2-mediated hyperfusion of mitochondria". Molecular Biology of the Cell. 28 (5): 600–612. PMID 28057766.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.