Protein-coding gene in the species Homo sapiens
Solute carrier family 25 member 46 is aprotein that in humans is encoded by theSLC25A46 gene . This protein is a member of theSLC25 mitochondrial solute carrier family . It is atransmembrane protein located in themitochondrial outer membrane involved inlipid transfer from theendoplasmic reticulum (ER) tomitochondria .[ 5] [ 6] Mutations in this gene result inneuropathy and optic atrophy .[ 7]
TheSLC25A46 gene is located on the q arm ofchromosome 5 in position 22.1 and spans 27,039 base pairs.[ 7] amino acids .[ 8] [ 9] exons and encodes amulti-pass integral membrane protein localized to the mitochondrial outer membrane.[ 10] [ 11] [ 12]
The encoded protein is an orphan transporter involved in lipid transfer from the endoplasmic reticulum to mitochondria.[ 13] [ 6] mitochondrial fission and prevents the formation of hyperfilamentous mitochondria. This protein forms acomplex with mitofilin (IMMT ) on the inner mitochondrial membrane, independent ofMFN2 .[ 5]
Clinical Significance [ edit ] Mutations in theSLC25A46 gene, inherited in anautosomal recessive manner, cause type 6Bhereditary motor and sensory neuropathy . Symptoms include early-onset optic atrophy, progressive visual loss, andperipheral sensorimotor neuropathy manifesting asaxonal Charcot-Marie-Tooth disease , with variable age at onset and severity.[ 11] [ 12]
Overexpression of this protein causes mitochondrial fragmentation whileknockdown of this protein causesmitochondrial hyperfusion and hyperfilamentous mitochondria due to decreased mitochondrial fission.[ 5] cellular senescence , impairedcellular respiration , destabilization of the MICOS (mitochondrial contact site and cristae organizing system) complex, loss of and shortenedcristae , altered ERmorphology , impairedcell migration , and changes in mitochondrialphospholipid composition.[ 6]
This proteininteracts withIMMT , 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.[ 11] [ 12] [ 6] SLC7A8 ,SLC10A1 ,SLC10A6 ,FHL3 ,FUNDC1 ,linc01142 ,LEPROTL1 ,ODF4 ,VMA21 ,MFSD14B ,PQLC1 ,HSD17B11 ,REEP2 ,REEP4 , andTOMM22 .[ 14] OPA1 andMFN2 .[ 6]
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