A comparative study on iron sources for mitochondrial haem synthesis including ferritin and models of transit pool species.
The rates of reaction of various exogenic iron(III) complexes with deuteroporphyrin IX in isolated mitochondria to form deuterohaem were measured. Ferritin was shown to supply iron readily for haem synthesis if the ferritin iron was reductively mobilised by the mitochondrial respiratory chain with succinate as substrate and FMN as mediator. In contrast, polynuclear complexes of iron(III) were able to form deuterohaem without added FMN. Rates of haem formation are about five times higher for the lowest polynuclear units than for ferritin. Sorbitol, gluconate, and bovine serum albumin were used as scavengers for polynuclear complexes with restricted size. Strong chelators of iron(II) compete favourably for deuterohaem formation, which supports the multistep mechanism for haem formation suggested by a priori arguments. Rates of deuterohaem formation were measured in homologous and heterologous systems of ferritins and mitochondria. Slightly differing rates of haem formation were shown to originate in different rates of iron mobilisation from the ferritins. The lack of species specificity in the interaction of ferritin with mitochondria also shows up in the linear dependence of ferritin binding on its bulk concentration as measured using 3H-labeled ferritin. Rates of haem formation are virtually the same in mitoplasts and mitochondria which indicates insignificant influences of the outer membrane. The hypothesis of low polynuclears as major components of the intracellular transit iron pool implies that both ferritin and transit iron pool species are largely equivalent sources of iron for mitochondrial haem synthesis.
D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism*; D005297:Ferrozine / Q000378:metabolism; D005486:Flavin Mononucleotide / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis*; D006736:Horses; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D008930:Mitochondria, Liver / Q000378:metabolism*; D008956:Models, Chemical; D008995:Monoamine Oxidase / Q000378:metabolism; D010618:Phenanthrolines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000032:analysis
D010618:Phenanthrolines; D005297:Ferrozine; D006418:Heme; C006686:bathophenanthroline; D005486:Flavin Mononucleotide; D005293:Ferritins; D007501:Iron; D008995:Monoamine Oxidase; D003576:Electron Transport Complex IV