Heme oxygenase and iron: from bacteria to humans

Abstract

Iron and iron-containing prosthetic groups are involved in many fundamental processes that constitute life. One of the biologically most important iron-containing groups is heme, in which an iron atom is co-ordinated to a protoporphyrin ring. Heme proteins have a wide range of functions, participating in a vast repertoire of biochemical reactions. Due to its abundance, heme also serves as an important source of iron. Enzymatic degradation of heme usually involves its oxidative cleavage by heme oxygenase. Not surprisingly, heme oxygenase activity is present in organisms across different domains and kingdoms. This review summarises the current knowledge in the dynamic relationship between heme oxygenase and iron in metabolism and in the clinical context.

CO metabolism, sensing, and signaling

“…Both the human case of HO-1 deficiency and the HO-1 knockout mouse model provide clear evidence of a role of HO-1 in the heme degradation, in the maintenance of vascular and tissue iron homeostasis, and in the systemic responses to stress [21,41,56]. Remarkably, the protective role of HO-1 has been demonstrated by both preclinical studies using HO-1 knockout and by analysis of transgenic mice models [42].…”

“…Recently, the critical physiological role of the HO/CO system has been highlighted by several lines of evidence: (i) the description of the first and unique case of human HO-1 deficiency; (ii) the identification of human functional HO-1 polymorphisms; (iii) the production of knockout animal models by targeted deletion of HO-1 and HO-2 genes; (iv) the production of transgenic animals overexpressing HO in a tissue-specific manner; (v) the HO-1 and HO-2 genes knockdown by RNA interference; and (vi) the modulation of HO activity by pharmacological approaches (i.e., HO activators and mimetics, porphyrin and nonporphyrin-based HO inhibitors) [21,41,42,56]. Both the human case of HO-1 deficiency and the HO-1 knockout mouse model provide clear evidence of a role of HO-1 in the heme degradation, in the maintenance of vascular and tissue iron homeostasis, and in the systemic responses to stress [21,41,56].…”

Regulons of Three Pseudomonas syringae pv. tomato DC3000 Iron Starvation Sigma Factors

“…PSPTO_1286 regulates PSPTO_1283, predicted to encode a heme oxygenase. Proteins of this class are often involved in the degradation of chelators to extract the iron (17). Three additional locations were also enriched in the PSPTO_1209 ChIP-seq experiments, but we were unable to detect regulation of the genes downstream of them.…”

Hemin toxicity: a preventable source of brain damage following hemorrhagic stroke

“…Once biliverdin has been formed, it is rapidly metabolized to bilirubin by biliverdin reductase. 16,33 Two active isomers of HO are found in the brain: heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). HO-1, also known as heat shock protein 32 (HSP32), is strongly expressed by astrocytes and microglia but is weakly expressed by neurons.…”

“…Inside these cells, hemin is degraded by heme oxygenases that cleave the porphyrin ring to biliverdin and CO, thereby releasing iron. This unbound iron can be stored within ferritin, 16 which eventually becomes saturated with iron and is degraded in lysosomes to hemosiderin, which is redox-inert. 17 A considerable body of research has been devoted to understanding how hemin contributes to the secondary brain damage that accompanies hemorrhagic stroke.…”