Abstract：
:Heme biosynthesis consists of a series of eight enzymatic reactions that originate in mitochondria and continue in the cytosol before returning to mitochondria. Although these core enzymes are well studied, additional mitochondrial transporters and regulatory factors are predicted to be required. To discover such unknown components, we utilized a large-scale computational screen to identify mitochondrial proteins whose transcripts consistently coexpress with the core machinery of heme biosynthesis. We identified SLC25A39, SLC22A4, and TMEM14C, which are putative mitochondrial transporters, as well as C1orf69 and ISCA1, which are iron-sulfur cluster proteins. Targeted knockdowns of all five genes in zebrafish resulted in profound anemia without impacting erythroid lineage specification. Moreover, silencing of Slc25a39 in murine erythroleukemia cells impaired iron incorporation into protoporphyrin IX, and vertebrate Slc25a39 complemented an iron homeostasis defect in the orthologous yeast mtm1Delta deletion mutant. Our results advance the molecular understanding of heme biosynthesis and offer promising candidate genes for inherited anemias.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Nilsson R,Schultz IJ,Pierce EL,Soltis KA,Naranuntarat A,Ward DM,Baughman JM,Paradkar PN,Kingsley PD,Culotta VC,Kaplan J,Palis J,Paw BH,Mootha VKdoi
10.1016/j.cmet.2009.06.012subject
Has Abstractpub_date
2009-08-01 00:00:00pages
119-30issue
2eissn
1550-4131issn
1932-7420pii
S1550-4131(09)00196-Xjournal_volume
10pub_type
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