{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough the initial query mentioned “POM121L9P,” the provided literature does not describe any function for that gene; rather, these studies collectively elucidate the multifaceted roles of myoglobin in mammalian tissues. Traditionally recognized as an intracellular oxygen‐reservoir in cardiac and slow‐twitch skeletal muscle, myoglobin also functions as a hypoxia‐dependent nitrite reductase that generates nitric oxide. This process modulates mitochondrial respiration and confers cytoprotection during ischemia–reperfusion injury, while also participating in hypoxic vasodilation in the heart and even in the vasculature of certain species."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical oxygen‐binding role, myoglobin plays critical protective and regulatory functions. It attenuates oxidative stress by scavenging reactive oxygen and nitrogen species, thereby preserving cardiac contractility and energy homeostasis. Furthermore, studies in myoglobin‐deficient models demonstrate that loss of this protein induces a compensatory shift in substrate utilization—from fatty acids to glucose oxidation—to mitigate the detrimental effects of impaired oxygen delivery and nitrosative stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, myoglobin contributes to vascular function and broader metabolic regulation. Its expression can influence vascular relaxation and angiogenesis, as well as impact tumor biology and brown adipose tissue thermogenesis. Hormonal and exercise‐mediated signaling further modulate myoglobin levels, underscoring its role in diverse processes including adaptive cardiac remodeling, attenuation of lipotoxicity, and the regulation of energy expenditure in thermogenic tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAnimal model studies further reveal that changes in myoglobin expression—whether through genetic ablation or overexpression—elicit compensatory mechanisms governing cardiac energetics, substrate selection, and gene regulation in response to hemodynamic and hypoxic stress. Such adaptations reinforce myoglobin’s integrative role as a cytoplasmic buffer for nitric oxide and mediator of oxygen-dependent metabolic pathways, thereby ensuring tissue protection and functional resilience under diverse physiologic and pathologic conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ulrike B Hendgen-Cotta, Marc W Merx, Sruti Shiva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0801336105"}], "href": "https://doi.org/10.1073/pnas.0801336105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18632562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18632562"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shane B Kanatous, Pradeep P A Mammen, Paul B Rosenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia reprograms calcium signaling and regulates myoglobin expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00428.2008"}], "href": "https://doi.org/10.1152/ajpcell.00428.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19005161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19005161"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Matthias Totzeck, Ulrike B Hendgen-Cotta, Peter Luedike, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.111.087155"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.111.087155"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22685116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22685116"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ulrich Flögel, Axel Gödecke, Lars-Oliver Klotz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of myoglobin in the antioxidant defense of the heart."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.03-1382fje"}], "href": "https://doi.org/10.1096/fj.03-1382fje"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15132981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15132981"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marc W Merx, Axel Gödecke, Ulrich Flögel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxygen supply and nitric oxide scavenging by myoglobin contribute to exercise endurance and cardiac function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.04-2886fje"}], "href": "https://doi.org/10.1096/fj.04-2886fje"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15817640"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15817640"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ulrich Flögel, Tim Laussmann, Axel Gödecke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of myoglobin causes a switch in cardiac substrate selection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.RES.0000165481.36288.d2"}], "href": "https://doi.org/10.1161/01.RES.0000165481.36288.d2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15817884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15817884"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ulrike B Hendgen-Cotta, Sonja Esfeld, Cristina Coman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel physiological role for cardiac myoglobin in lipid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep43219"}], "href": "https://doi.org/10.1038/srep43219"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28230173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28230173"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Satu Mänttäri, Katja Anttila, Matti Järvilehto "}, {"type": "b", "children": [{"type": "t", "text": "Testosterone stimulates myoglobin expression in different muscles of the mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Comp Physiol B (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00360-008-0280-x"}], "href": "https://doi.org/10.1007/s00360-008-0280-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18548256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18548256"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Julian O M Ormerod, Houman Ashrafian, Abdul R Maher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of vascular myoglobin in nitrite-mediated blood vessel relaxation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvq299"}], "href": "https://doi.org/10.1093/cvr/cvq299"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20889759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20889759"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Chad K Nicholson, Jonathan P Lambert, Chi-Wing Chow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia-reperfusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2013.08.002"}], "href": "https://doi.org/10.1016/j.yjmcc.2013.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23962643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23962643"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Anne Bicker, Dimo Dietrich, Eva Gleixner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extensive transcriptional complexity during hypoxia-regulated expression of the myoglobin gene in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt438"}], "href": "https://doi.org/10.1093/hmg/ddt438"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24026678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24026678"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Eva L Peters, Sandra M van der Linde, Ilse S P Vogel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IGF-1 Attenuates Hypoxia-Induced Atrophy but Inhibits Myoglobin Expression in C2C12 Skeletal Muscle Myotubes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms18091889"}], "href": "https://doi.org/10.3390/ijms18091889"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28862673"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28862673"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Mostafa A Aboouf, Julia Armbruster, Markus Thiersch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myoglobin, expressed in brown adipose tissue of mice, regulates the content and activity of mitochondria and lipid droplets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Biol Lipids (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2021.159026"}], "href": "https://doi.org/10.1016/j.bbalip.2021.159026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34384891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34384891"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Mostafa A Aboouf, Thomas A Gorr, Nadia M Hamdy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myoglobin in Brown Adipose Tissue: A Multifaceted Player in Thermogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells12182240"}], "href": "https://doi.org/10.3390/cells12182240"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37759463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37759463"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Axel Gödecke, Andre Molojavyi, Jacqueline Heger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myoglobin protects the heart from inducible nitric-oxide synthase (iNOS)-mediated nitrosative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M302573200"}], "href": "https://doi.org/10.1074/jbc.M302573200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12665503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12665503"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Carsten Wunderlich, Ulrich Flögel, Axel Gödecke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acute inhibition of myoglobin impairs contractility and energy state of iNOS-overexpressing hearts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.RES.0000079026.70629.E5"}], "href": "https://doi.org/10.1161/01.RES.0000079026.70629.E5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12775582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12775582"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Pradeep P A Mammen, Shane B Kanatous, Ivan S Yuhanna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Heart Circ Physiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpheart.00147.2003"}], "href": "https://doi.org/10.1152/ajpheart.00147.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12881221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12881221"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Wei Li, Thomas Jue, John Edwards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Changes in NO bioavailability regulate cardiac O2 consumption: control by intramitochondrial SOD2 and intracellular myoglobin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Heart Circ Physiol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpheart.00730.2003"}], "href": "https://doi.org/10.1152/ajpheart.00730.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12919935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12919935"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Erkki Liimatta, Anu M Kantola, Ilmo E Hassinen "}, {"type": "b", "children": [{"type": "t", "text": "Dual probe fluorescence monitoring of intracellular free calcium during ischemia in mouse heart by using continuous compensation for pH dependence of the dissociation constant of Fura-2, and the interference of myoglobin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem Biophys Methods (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbbm.2007.01.006"}], "href": "https://doi.org/10.1016/j.jbbm.2007.01.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17316820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17316820"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Andrei Molojavyi, Antje Lindecke, Annika Raupach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myoglobin-deficient mice activate a distinct cardiac gene expression program in response to isoproterenol-induced hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Physiol Genomics (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/physiolgenomics.90297.2008"}], "href": "https://doi.org/10.1152/physiolgenomics.90297.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20145201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20145201"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Joshua K Meisner, Ji Song, Brian H Annex, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myoglobin overexpression inhibits reperfusion in the ischemic mouse hindlimb through impaired angiogenesis but not arteriogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2013.08.005"}], "href": "https://doi.org/10.1016/j.ajpath.2013.08.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24095922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24095922"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Mostafa A Aboouf, Julia Armbruster, Franco Guscetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endogenous myoglobin expression in mouse models of mammary carcinoma reduces hypoxia and metastasis in PyMT mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-023-34614-w"}], "href": "https://doi.org/10.1038/s41598-023-34614-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37161046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37161046"}]}]}]}