Ferritin complex

Abstract: Ferritin was isolated from the livers and brains of two groups of rats, one of which was fed aluminum chloride (100 microM) for 1 year in the drinking water. Brain tissue contained about one-third of the amount of ferritin found in the liver. While brain ferritin from normal rats contained 42.1 +/- 14.3 mol of aluminum, that from the aluminum-fed group contained 115.4 +/- 48.3 mol of aluminum per mol of ferritin. Liver ferritin from both groups contained similar amounts of both aluminum and iron, and the amounts were less than that found associated with brain ferritin. Ferritin isolated from the brains of patients who died of Alzheimer disease contained more aluminum and more iron than that from age-matched controls. Human brain ferritin is composed of two types of subunits--about 70% heavy chain (Mr, 22,000) and 30% light chain (Mr, 19,500). The isoelectric focusing pattern of human brain ferritin was considerably different from that of human liver. Only 5 of the 20 brain ferritin bands migrated similarly to the acidic isoferritins from the liver, and the major component of brain ferritin, representing 30% of the total ferritin, had a pI of 8.0.

Abstract: Plasma ferritin is an important extracellular iron storage molecule, whose concentration increases drastically in cancer and infection. During infection, the pathogen usurps host iron for its survival and pathogenicity; hence, maintenance of the plasma ferritin level during infection is a crucial host defence mechanism. In this study, the horseshoe crab plasma ferritin complex was purified, characterized, and its involvement in innate immune defence was investigated. The plasma ferritin appears as a 21-kDa subunit on SDS-PAGE. Full-length ferritin-H cDNAs (CrFer-H1 and CrFerH2) were cloned. Analysis of the 5′ UTR indicates the existence of a functional iron-response element, suggesting that both the CrFer-H genes may be post-transcriptionally regulated. Northern analysis shows that the CrFer-H is ubiquitously expressed. Within 3 h of lipopolysaccharide challenge, the gene is up-regulated by > 12-fold. In contrast, iron-loading did not result in any significant change. When challenged with Pseudomonas aeruginosa, the plasma ferritin disappeared between 6–48 h and re-appeared thereafter, suggesting that during infection, ferritin may be concealed intracellularly as it withholds iron from the invading pathogen. Taken together, these results provide insights into the importance of plasma ferritin as an evolutionarily conserved molecule for the iron-withholding strategy of innate immunity.

Abstract: Iron is an essential nutrient for mitochondrial metabolic processes, including mitochondrial respiration. Ferritin complexes store excess iron and protect cells from iron toxicity. Therefore, iron stored in the ferritin complex might be utilized under iron-depleted conditions. In this study, we show that the inhibition of lysosome-dependent protein degradation by bafilomycin A1 and the knockdown of NCOA4, an autophagic receptor for ferritin, reduced mitochondrial respiration, respiratory chain complex assembly, and membrane potential under iron-sufficient conditions. However, autophagy did not contribute to degradation of the ferritin complex under iron-sufficient conditions. Knockout of the ferritin light chain, a subunit of the ferritin complex, inhibited ferritin degradation by decreasing interactions with NCOA4. However, ferritin light chain knockout did not affect mitochondrial functions under iron-sufficient conditions, and ferritin light chain knockout cells showed a rapid reduction of mitochondrial functions compared with wild-type cells under iron-depleted conditions. These results indicate that the constitutive degradation of the ferritin complex contributes to the maintenance of mitochondrial functions.