AUTHOR=Anbalagan Savani 

TITLE=Hemoglobin as an oxygen gasoreceptor

JOURNAL=Acta Biochimica Polonica

VOLUME=Volume 72 - 2025

YEAR=2025

URL=https://www.frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2025.15546

DOI=10.3389/abp.2025.15546

ISSN=1734-154X

ABSTRACT=In most vertebrates, hemoglobin’s primary function is to transport oxygen and carbon dioxide. Hemoglobin is also expressed in cells such as dopaminergic neurons and chondrocytes, as well as in organelles such as mitochondria. Depending on its location, hemoglobin subunits can interact with proteins involved in various functions, including anion exchange, nitric oxide synthesis, and ATP synthesis. These interactions suggest that hemoglobin has diverse regulatory roles beyond gas transport. During hypoxia and an excess of nitrite and protons, deoxygenated hemoglobin exhibits nitrite reductase activity and produces nitric oxide, a gaseous signaling molecule. Hemoglobin-derived nitric oxide is associated with vasodilation in mammals and the inhibition of mitochondrial respiration in cell cultures. This raises the question of whether hemoglobin functions as a gasoreceptor in these cells or organelles. The HIF1α/PHD2 pathway in mammals and cysteine oxidases in plants are largely responsible for sensing hypoxia, but the identity of oxygen gasoreceptors analogous to the mammalian nitric oxide gasoreceptor soluble guanylate cyclase and the plant ethylene gasoreceptor kinases remains unknown. Since the heme-based dual oxygen-binding and catalytic domain emerged earlier than the allosteric regions, I propose hemoglobin as an oxygen proto-gasoreceptor derivative. Furthermore, since hemoglobin interacts with and regulates proteins depending on its oxygen binding state, I propose that hemoglobin functions as an oxygen gasoreceptor in split-component signal transduction systems. Recognizing hemoglobin as a gasoreceptor will expand the emerging field of gasocrinology to encompass gases that were previously considered primarily metabolic substrates.