The effects of inhibition of heme synthesis on the intracellular localization of iron in rat reticulocytes.
These studies assessed the fate and localization of incoming iron in 6-8-day rat reticulocytes during inhibition of heme synthesis by succinylacetone. Succinylacetone inhibition of heme synthesis increased iron uptake by increasing the rate of receptor recycling without affecting receptor KD for transferrin, transferrin uptake, or total receptor number. Its net effect was to amplify the number of surface transferrin receptors by recruitment of receptors from an intracellular pool. Despite increased iron influx in inhibited cells, only 2-4% of total incoming iron was diverted into ferritin. The majority of incoming iron (65-80%) in succinylacetone-inhibited cells was recovered in the stroma, where ultrastructural and enzymic analyses revealed it to be accumulated mainly in mitochondria. Intramitochondrial iron (70-75%) was localized mainly in the inner membrane fraction. Removal of succinylacetone restored heme synthesis, utilizing iron accumulated within mitochondria for its support. Thus, inhibition of heme synthesis in rat reticulocytes results in accumulation of incoming iron in a functional mobile intramitochondrial precursor iron pool used directly for heme synthesis. Under normal conditions, there is no significant intracellular or intramitochondrial iron pool in reticulocytes, which are therefore dependent upon continuous delivery of transferrin-bound iron to maintain heme synthesis. Ferritin plays an insignificant role in iron metabolism of reticulocytes.
Department of Anatomy, University of Connecticut Health Center, Farmington 06032.
M L
ML
Adams
I
I
Ostapiuk
J A
JA
Grasso
D000818:Animals; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D003593:Cytoplasm / Q000378:metabolism* / Q000648:ultrastructure; D006418:Heme / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006537:Heptanoates / Q000494:pharmacology; D007501:Iron / Q000097:blood*; D007504:Iron Radioisotopes; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D011990:Receptors, Transferrin / Q000187:drug effects / Q000378:metabolism; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
D006537:Heptanoates; D007504:Iron Radioisotopes; D011990:Receptors, Transferrin; D006418:Heme; C020804:succinylacetone; D007501:Iron