Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients have motor impairment, mental retardation, retinal degeneration and iron-deficiency anaemia. Because aberrant iron metabolism may cause neural and retinal degeneration, it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes after iron uptake by endocytosis of Fe(3+)-bound transferrin receptors, or after lysosomal degradation of ferritin-iron complexes and autophagic ingestion of iron-containing macromolecules, is the chief source of cellular iron. The divalent metal transporter protein DMT1 (also known as SLC11A2) is the only endosomal Fe(2+) transporter known at present and it is highly expressed in erythroid precursors. Genetic studies, however, suggest the existence of a DMT1-independent endosomal and lysosomal Fe(2+) transport protein. By measuring radiolabelled iron uptake, by monitoring the levels of cytosolic and intralysosomal iron and by directly patch-clamping the late endosomal and lysosomal membrane, here we show that TRPML1 functions as a Fe(2+) permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair the ability of TRPML1 to permeate Fe(2+) at varying degrees, which correlate well with the disease severity. A comparison of TRPML1(-/- )ML4 and control human skin fibroblasts showed a reduction in cytosolic Fe(2+) levels, an increase in intralysosomal Fe(2+) levels and an accumulation of lipofuscin-like molecules in TRPML1(-/-) cells. We propose that TRPML1 mediates a mechanism by which Fe(2+) is released from late endosomes and lysosomes. Our results indicate that impaired iron transport may contribute to both haematological and degenerative symptoms of ML4 patients.
 ...
PMID:The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. 1879 1

Emerging evidence has displayed that oxygen free radicals especially ones promoted by "free" iron play an important role in the development of alcoholic liver disease (ALD). Naturally-occurring quercetin has been reported to prevent ALD and iron overload-induced damage aside from the "free" iron. The purpose was to explore the potential mechanisms by which quercetin arrests alcohol-induced "free" iron disorder. Chronic alcohol (30% of total calories) or iron (0.2%)-fed adult male C57BL/J mice for 15 weeks resulted in significantly elevated levels of hepatic iron, labile iron pool-Fe and serum non-transferrin bound iron, accompanied with sustained oxidative damage. The hepatotoxicity was further exacerbated by ethanol and iron. Quercetin (100 mg/kg. body weight) alleviated the detrimental effects induced by ethanol and/or iron. The expressions of divalent metal transporter 1, zinc transporter member 14, mucolipin 1, transferrin receptor 1 (TfR1) and ferritin were up-regulated by ethanol and/or iron, which were partially normalized by quercetin. Quercetin prevented ethanol-induced hepatotoxicity, which may be partially attributed to the alleviated disorder of bound iron and "free" iron. The significant suppression of ethanol-stimulated molecules for "free" iron uptake and release may contribute to the hepatoprotective effect of quercetin, although TfR1-mediated physiological pathway of iron uptake also played a role.
 ...
PMID:Quercetin attenuates chronic ethanol hepatotoxicity: implication of "free" iron uptake and release. 2456 67