Lack of heme synthesis in a free-living eukaryote.
In most free-living eukaryotes studied thus far, heme is synthesized from a series of intermediates through a well defined evolutionarily conserved pathway. We found that free-living worms, including the model genetic organism Caenorhabditis elegans, and parasitic helminths are unable to synthesize heme de novo, even though these animals contain hemoproteins that function in key biological processes. Radioisotope, fluorescence labeling, and heme analog studies suggest that C. elegans acquires heme from exogenous sources. Iron-deprived worms were unable to grow in the presence of adequate heme unless rescued by increasing heme levels in the growth medium. These data indicate that although worms use dietary heme for incorporation into hemoproteins, ingested heme is also used as an iron source when iron is limiting. Our results provide a biochemical basis for the dependence of worm growth and development on heme, and they suggest that pharmacologic targeting of heme transport pathways in worms could be an important control measure for helminthic infections.
Rao
Anita U
AU
Department of Animal and Avian Sciences and Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Carta
Lynn K
LK
Lesuisse
Emmanuel
E
Hamza
Iqbal
I
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis; D003470:Culture Media; D016678:Genome; D006418:Heme / Q000096:biosynthesis*; D006420:Hemeproteins / Q000096:biosynthesis; D008969:Molecular Sequence Data
D029742:Caenorhabditis elegans Proteins; D003470:Culture Media; D006420:Hemeproteins; D006418:Heme