TMEM14C is required for erythroid mitochondrial heme metabolism

Regulation of heme biosynthesis and transport in metazoa

“…These mutant mice had CPgenIII accumulation accompanied by reduced level of PPIX in the fetal liver. This observation was further validated by the rescue of heme defects with a PPIX analog, deuteroporphyrin IX, in Tmem14c-deficient cells [67]. As a transmembrane protein localized to the inner mitochondrial membrane, TMEM14C may mediate the import of PPgenIX into the mitochondrial matrix [67].…”

“…This observation was further validated by the rescue of heme defects with a PPIX analog, deuteroporphyrin IX, in Tmem14c-deficient cells [67]. As a transmembrane protein localized to the inner mitochondrial membrane, TMEM14C may mediate the import of PPgenIX into the mitochondrial matrix [67]. ecules and pathways have been identified to transport heme within and between cells (Table 1).…”

“…A recent report showed that PPgenIX may be transported to PPOX by transmembrane protein 14C (TMEM14C) [67]. TMEM14C was first identified by a large-scale bioinformatics analysis to co-express with heme synthesis genes [68].…”

“…Silencing of tmem14c with morpholinos resulted in profound anemia in zebrafish embryos [68]. Tmem14c-deficient mice die during embryonic development [67]. These mutant mice had CPgenIII accumulation accompanied by reduced level of PPIX in the fetal liver.…”

Splicing factor mutations in MDS RARS and MDS/MPN-RS-T

“…SLC25A38 is thought to be an amino acid transporter required for importing glycine across the inner mitochondrial membrane in the initial steps of heme synthesis. Although transmembrane protein 14C (TMEM14C) is also involved in the terminal steps of heme synthesis pathway [25], no mutations in this gene have been reported in congenital SAs so far.…”