Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes
Open Access
- 8 April 2014
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 5, 61
- https://doi.org/10.3389/fphar.2014.00061
Abstract
Heme (iron-protoporphyrin IX) is an essential co-factor involved in multiple biological processes: oxygen transport and storage, electron transfer, drug and steroid metabolism, signal transduction, and micro RNA processing. However, excess free-heme is highly toxic due to its ability to promote oxidative stress and lipid peroxidation, thus leading to membrane injury and, ultimately, apoptosis. Thus, heme metabolism needs to be finely regulated. Intracellular heme amount is controlled at multiple levels: synthesis, utilization by hemoproteins, degradation and both intracellular and intercellular trafficking.This review focuses on recent findings highlighting the importance of controlling intracellular heme levels to counteract heme-induced oxidative stress. The contributions of heme scavenging from the extracellular environment, heme synthesis and incorporation into hemoproteins, heme catabolism and heme transport in maintaining adequate intracellular heme content are discussed. Particular attention is put on the recently described mechanisms of heme trafficking through the plasma membrane mediated by specific heme importers and exporters. Finally, the involvement of genes orchestrating heme metabolism in several pathological conditions is illustrated and new therapeutic approaches aimed at controlling heme metabolism are discussed.Keywords
This publication has 144 references indexed in Scilit:
- Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damageCell Death & Differentiation, 2013
- ABCB6 Mutations Cause Ocular ColobomaAmerican Journal of Human Genetics, 2012
- Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorptionMolecular Genetics and Metabolism, 2011
- Mutations in FLVCR1 Cause Posterior Column Ataxia and Retinitis PigmentosaAmerican Journal of Human Genetics, 2010
- Porphyria cutanea tarda – When skin meets liverBest Practice & Research Clinical Gastroenterology, 2010
- Mutations in FLVCR2 Are Associated with Proliferative Vasculopathy and Hydranencephaly-Hydrocephaly Syndrome (Fowler Syndrome)American Journal of Human Genetics, 2010
- Systematic molecular genetic analysis of congenital sideroblastic anemia: Evidence for genetic heterogeneity and identification of novel mutationsPediatric Blood & Cancer, 2009
- Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association studyThe Lancet, 2008
- C-Terminal Deletions in the ALAS2 Gene Lead to Gain of Function and Cause X-linked Dominant Protoporphyria without Anemia or Iron OverloadAmerican Journal of Human Genetics, 2008
- Genome-wide atlas of gene expression in the adult mouse brainNature, 2006