title: Biological signaling by carbon monoxide and carbon monoxide-releasing molecules.
abstract: Carbon monoxide (CO) is continuously produced in mammalian cells during the degradation of heme. It is a stable gaseous molecule that reacts selectively with transition metals in a specific redox state, and these characteristics restrict the interaction of CO with defined biological targets that transduce its signaling activity. Because of the high affinity of CO for ferrous heme, these targets can be grouped into heme-containing proteins, representing a large variety of sensors and enzymes with a series of diverse function in the cell and the organism. Despite this notion, progress in identifying which of these targets are selective for CO has been slow and even the significance of elevated carbonmonoxy hemoglobin, a classical marker used to diagnose CO poisoning, is not well understood. This is also due to the lack of technologies capable of assessing in a comprehensive fashion the distribution and local levels of CO between the blood circulation, the tissue, and the mitochondria, one of the cellular compartments where CO exerts its signaling or detrimental effects. Nevertheless, the use of CO gas and CO-releasing molecules as pharmacological approaches in models of disease has provided new important information about the signaling properties of CO. In this review we will analyze the most salient effects of CO in biology and discuss how the binding of CO with key ferrous hemoproteins serves as a posttranslational modification that regulates important processes as diverse as aerobic metabolism, oxidative stress, and mitochondrial bioenergetics.
authors.affiliation: Inserm U955, Team 12, Créteil, France; and Faculty of Medicine, Université Paris Est, Créteil, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Motterlini
authors.affiliation: Inserm U955, Team 12, Créteil, France; and Faculty of Medicine, Université Paris Est, Créteil, France roberta.foresti@inserm.fr.
authors.forename: Roberta
authors.initials: R
authors.lastname: Foresti
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D001808:Blood Vessels / Q000502:physiology*; D002248:Carbon Monoxide / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D006418:Heme; D002248:Carbon Monoxide
keywords: carbon monoxide; carbon monoxide-releasing molecules (CO-RMs); cytochrome-c oxidase; hemoglobin; hemoproteins; mitochondria