Target intelligence / Profile preview

Mitochondrial folate transporter (SLC25A32)

Target
SLC25A32
Molecular classification
Transporter, Solute carrier family member, Mitochondrial carrier protein
01

Overview

The **mitochondrial folate transporter** (SLC25A32) is a member of the mitochondrial carrier protein family located in the inner mitochondrial membrane. Its primary role is the import of tetrahydrofolate (THF) and potentially FAD (flavin adenine dinucleotide) into the mitochondrial matrix, supporting fundamental biochemical processes such as one-carbon metabolism, nucleotide (purine, thymidylate) biosynthesis, methylation reactions, and glycine catabolism. Defects in SLC25A32 are associated with human diseases including riboflavin-responsive exercise intolerance and folate-resistant neural tube defects[1][2][3]. Riboflavin supplementation can partly ameliorate symptoms linked to FAD deficiency, whereas formate (not folic acid) supplementation has been shown in mouse models to rescue some neural tube closure defects caused by SLC25A32 mutations[2]. SLC25A32 has also been implicated in cancer biology and bone health in population studies[2][3].

Other names
Solute carrier family 25 member 32MFTMitochondrial FAD transporterMFTCGlycine auxotroph BRREI (riboflavin-responsive exercise intolerance protein)Mitochondrial folate carrier
02

Mechanism of action

Restoration of FAD levels (riboflavin supplementation corrects FAD deficiency due to SLC25A32 mutations); Rescue of mitochondrial one-carbon metabolism via formate supplementation (shown in mouse models for neural tube defects)

03

Biological functions

Folate transport across the mitochondrial inner membraneFlavin adenine dinucleotide (FAD) transportOne-carbon (1C) metabolismDNA replication, methylation, and repairPurine and thymidylate biosynthesisHomocysteine remethylation to methionineGlycine homeostasis
04

Disease associations

Neural tube defectRiboflavin-responsive exercise intoleranceMitochondrial DNA maintenance defectCancer (expression changes reported in ovarian and breast cancers)Bone fracture risk (association studies)Other rare mitochondrial disorders with metabolic features
05

Safety considerations

Notable challenge: Some neural tube defects are resistant to folic acid supplementationPossible mitochondrial dysfunction with broad metabolic effects; precise safety concerns depend on context (gene therapy, targeted modulation, etc.)
06

Interacting drugs

Riboflavin (vitamin B2)

2 more in the full profile.

07

Biomarkers

Mutations in SLC25A32 geneDecreased mitochondrial FAD or folate transport activityPlasma folate levels (possibly influenced by SLC25A32 variants)Metabolic evidence of DNA synthesis or methylation defects (indirect in disease)

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