{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:38:21Z","timestamp":1793129901277,"version":"4.5.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["AoE\/M\/707-18"],"award-info":[{"award-number":["AoE\/M\/707-18"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004377","name":"Hong Kong Polytechnic University","doi-asserted-by":"publisher","award":["P0040979"],"award-info":[{"award-number":["P0040979"]}],"id":[{"id":"10.13039\/501100004377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92357305, 81970675"],"award-info":[{"award-number":["92357305, 81970675"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Municipal Science and Technology Innovation Commission Basic Research General Programme"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-024-53006-w","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T17:01:40Z","timestamp":1728061300000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":163,"title":["MDM2 induces pro-inflammatory and glycolytic responses in M1 macrophages by integrating iNOS-nitric oxide and HIF-1\u03b1 pathways in mice"],"prefix":"10.1038","volume":"15","author":[{"given":"Kelvin Ka-lok","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moinul","family":"Hoque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-2356","authenticated-orcid":false,"given":"Gloria Hoi Yee","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-7160","authenticated-orcid":false,"given":"Qizhou","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kekao","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongxi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7451-0386","authenticated-orcid":false,"given":"Hailong","family":"Piao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0668-033X","authenticated-orcid":false,"given":"Aimin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7525-5812","authenticated-orcid":false,"given":"Hannah Xiaoyan","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7274-0839","authenticated-orcid":false,"given":"Kenneth King-yip","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"53006_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29731-5","volume":"13","author":"Q Lian","year":"2022","unstructured":"Lian, Q. et al. Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model. Nat. Commun. 13, 2028 (2022).","journal-title":"Nat. Commun."},{"key":"53006_CR2","doi-asserted-by":"publisher","first-page":"3733","DOI":"10.4049\/jimmunol.181.6.3733","volume":"181","author":"M Benoit","year":"2008","unstructured":"Benoit, M., Desnues, B. & Mege, J. L. Macrophage polarization in bacterial infections. J. Immunol. 181, 3733\u20133739 (2008).","journal-title":"J. Immunol."},{"key":"53006_CR3","doi-asserted-by":"publisher","first-page":"6425","DOI":"10.1002\/jcp.26429","volume":"233","author":"A Shapouri-Moghaddam","year":"2018","unstructured":"Shapouri-Moghaddam, A. et al. Macrophage plasticity, polarization, and function in health and disease. J. Cell Physiol. 233, 6425\u20136440 (2018).","journal-title":"J. Cell Physiol."},{"key":"53006_CR4","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.cmet.2020.08.002","volume":"32","author":"AF McGettrick","year":"2020","unstructured":"McGettrick, A. F. & O\u2019Neill, L. A. J. The role of HIF in immunity and inflammation. Cell Metab. 32, 524\u2013536 (2020).","journal-title":"Cell Metab."},{"key":"53006_CR5","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9029327","volume":"2017","author":"T Wang","year":"2017","unstructured":"Wang, T. et al. HIF1alpha-induced glycolysis metabolism is essential to the activation of inflammatory macrophages. Mediators Inflamm. 2017, 9029327 (2017).","journal-title":"Mediators Inflamm."},{"key":"53006_CR6","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nature11986","volume":"496","author":"GM Tannahill","year":"2013","unstructured":"Tannahill, G. M. et al. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature 496, 238\u2013242 (2013).","journal-title":"Nature"},{"key":"53006_CR7","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.cmet.2014.12.005","volume":"21","author":"EM Palsson-McDermott","year":"2015","unstructured":"Palsson-McDermott, E. M. et al. Pyruvate kinase M2 regulates Hif-1alpha activity and IL-1beta induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 21, 65\u201380 (2015).","journal-title":"Cell Metab."},{"key":"53006_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101501","volume":"298","author":"NC Williams","year":"2022","unstructured":"Williams, N. C. et al. Signaling metabolite L-2-hydroxyglutarate activates the transcription factor HIF-1alpha in lipopolysaccharide-activated macrophages. J. Biol. Chem. 298, 101501 (2022).","journal-title":"J. Biol. Chem."},{"key":"53006_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32871-3","volume":"13","author":"T Feng","year":"2022","unstructured":"Feng, T. et al. Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2. Nat. Commun. 13, 5208 (2022).","journal-title":"Nat. Commun."},{"key":"53006_CR10","doi-asserted-by":"publisher","first-page":"e74741","DOI":"10.1371\/journal.pone.0074741","volume":"8","author":"JA Lehman","year":"2013","unstructured":"Lehman, J. A. et al. Serdemetan antagonizes the Mdm2-HIF1alpha axis leading to decreased levels of glycolytic enzymes. PloS one 8, e74741 (2013).","journal-title":"PloS one"},{"key":"53006_CR11","doi-asserted-by":"publisher","first-page":"13595","DOI":"10.1074\/jbc.C200694200","volume":"278","author":"D Chen","year":"2003","unstructured":"Chen, D., Li, M., Luo, J. & Gu, W. Direct interactions between HIF-1 alpha and Mdm2 modulate p53 function. J. Biol. Chem. 278, 13595\u201313598 (2003).","journal-title":"J. Biol. Chem."},{"key":"53006_CR12","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.3390\/jcm8091350","volume":"8","author":"NR Han","year":"2019","unstructured":"Han, N. R., Moon, P. D., Kim, H. M. & Jeong, H. J. TSLP exacerbates septic inflammation via murine double minute 2 (MDM2) signaling pathway. J. Clin. Med. 8, 1350 (2019).","journal-title":"J. Clin. Med"},{"key":"53006_CR13","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1038\/ki.2011.482","volume":"81","author":"SR Mulay","year":"2012","unstructured":"Mulay, S. R., Thomasova, D., Ryu, M. & Anders, H. J. MDM2 (murine double minute-2) links inflammation and tubular cell healing during acute kidney injury in mice. Kidney Int 81, 1199\u20131211 (2012).","journal-title":"Kidney Int"},{"key":"53006_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2020.05.020","volume":"305","author":"Y Zeng","year":"2020","unstructured":"Zeng, Y., Xu, J., Hua, Y. Q., Peng, Y. & Xu, X. L. MDM2 contributes to oxidized low-density lipoprotein-induced inflammation through modulation of mitochondrial damage in endothelial cells. Atherosclerosis 305, 1\u20139 (2020).","journal-title":"Atherosclerosis"},{"key":"53006_CR15","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41590-021-00888-3","volume":"22","author":"J Zhou","year":"2021","unstructured":"Zhou, J. et al. The ubiquitin ligase MDM2 sustains STAT5 stability to control T cell-mediated antitumor immunity. Nat. Immunol. 22, 460\u2013470 (2021).","journal-title":"Nat. Immunol."},{"key":"53006_CR16","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/cdd.2014.212","volume":"22","author":"L Li","year":"2015","unstructured":"Li, L. et al. A unique role for p53 in the regulation of M2 macrophage polarization. Cell Death Differ. 22, 1081\u20131093 (2015).","journal-title":"Cell Death Differ."},{"key":"53006_CR17","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.imbio.2014.08.010","volume":"220","author":"E Odkhuu","year":"2015","unstructured":"Odkhuu, E. et al. Lipopolysaccharide downregulates the expression of p53 through activation of MDM2 and enhances activation of nuclear factor-kappa B. Immunobiology 220, 136\u2013141 (2015).","journal-title":"Immunobiology"},{"key":"53006_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1546-9","volume":"15","author":"M Genin","year":"2015","unstructured":"Genin, M., Clement, F., Fattaccioli, A., Raes, M. & Michiels, C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer 15, 577 (2015).","journal-title":"BMC Cancer"},{"key":"53006_CR19","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.stem.2010.09.013","volume":"7","author":"HA Abbas","year":"2010","unstructured":"Abbas, H. A. et al. Mdm2 is required for survival of hematopoietic stem cells\/progenitors via dampening of ROS-induced p53 activity. Cell Stem Cell 7, 606\u2013617 (2010).","journal-title":"Cell Stem Cell"},{"key":"53006_CR20","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.molmet.2019.10.002","volume":"33","author":"M Lacroix","year":"2020","unstructured":"Lacroix, M., Riscal, R., Arena, G., Linares, L. K. & Le Cam, L. Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer. Mol. Metab. 33, 2\u201322 (2020).","journal-title":"Mol. Metab."},{"key":"53006_CR21","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.molcel.2018.01.023","volume":"69","author":"G Arena","year":"2018","unstructured":"Arena, G. et al. Mitochondrial MDM2 regulates respiratory complex I activity independently of p53. Mol. Cell 69, 594\u2013609.e598 (2018).","journal-title":"Mol. Cell"},{"key":"53006_CR22","doi-asserted-by":"publisher","first-page":"3367","DOI":"10.1182\/blood.V99.9.3367","volume":"99","author":"L Gu","year":"2002","unstructured":"Gu, L., Findley, H. W. & Zhou, M. MDM2 induces NF-kappaB\/p65 expression transcriptionally through Sp1-binding sites: a novel, p53-independent role of MDM2 in doxorubicin resistance in acute lymphoblastic leukemia. Blood 99, 3367\u20133375 (2002).","journal-title":"Blood"},{"key":"53006_CR23","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1593\/neo.121534","volume":"14","author":"D Thomasova","year":"2012","unstructured":"Thomasova, D., Mulay, S. R., Bruns, H. & Anders, H. J. p53-independent roles of MDM2 in NF-kappaB signaling: implications for cancer therapy, wound healing, and autoimmune diseases. Neoplasia 14, 1097\u20131101 (2012).","journal-title":"Neoplasia"},{"key":"53006_CR24","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/387296a0","volume":"387","author":"Y Haupt","year":"1997","unstructured":"Haupt, Y., Maya, R., Kazaz, A. & Oren, M. Mdm2 promotes the rapid degradation of p53. Nature 387, 296\u2013299 (1997).","journal-title":"Nature"},{"key":"53006_CR25","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1126\/science.285.5434.1733","volume":"285","author":"PG Komarov","year":"1999","unstructured":"Komarov, P. G. et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285, 1733\u20131737 (1999).","journal-title":"Science"},{"key":"53006_CR26","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1111\/j.1749-6632.2002.tb04680.x","volume":"973","author":"JP Piret","year":"2002","unstructured":"Piret, J. P., Mottet, D., Raes, M. & Michiels, C. CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2. Ann. N. Y Acad. Sci. 973, 443\u2013447 (2002).","journal-title":"Ann. N. Y Acad. Sci."},{"key":"53006_CR27","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.molcel.2007.02.024","volume":"26","author":"F Li","year":"2007","unstructured":"Li, F. et al. Regulation of HIF-1alpha stability through S-nitrosylation. Mol. Cell 26, 63\u201374 (2007).","journal-title":"Mol. Cell"},{"key":"53006_CR28","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.3390\/cancers12092349","volume":"12","author":"C Sanhueza","year":"2020","unstructured":"Sanhueza, C. et al. Caveolin-1-mediated tumor suppression is linked to reduced HIF1\u03b1 S-nitrosylation and transcriptional activity in hypoxia. Cancers (Basel) 12, 2349 (2020).","journal-title":"Cancers (Basel)"},{"key":"53006_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7676","volume":"6","author":"G Lu","year":"2015","unstructured":"Lu, G. et al. Myeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization. Nat. Commun. 6, 6676 (2015).","journal-title":"Nat. Commun."},{"key":"53006_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14433-7","volume":"11","author":"EM Palmieri","year":"2020","unstructured":"Palmieri, E. M. et al. Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase. Nat. Commun. 11, 698 (2020).","journal-title":"Nat. Commun."},{"key":"53006_CR31","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.bbrc.2011.04.103","volume":"409","author":"K Matsumoto","year":"2011","unstructured":"Matsumoto, K. et al. The ECS(SPSB) E3 ubiquitin ligase is the master regulator of the lifetime of inducible nitric-oxide synthase. Biochem Biophys. Res Commun. 409, 46\u201351 (2011).","journal-title":"Biochem Biophys. Res Commun."},{"key":"53006_CR32","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cellimm.2009.03.009","volume":"258","author":"L Chen","year":"2009","unstructured":"Chen, L. et al. CHIP facilitates ubiquitination of inducible nitric oxide synthase and promotes its proteasomal degradation. Cell Immunol. 258, 38\u201343 (2009).","journal-title":"Cell Immunol."},{"key":"53006_CR33","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1083\/jcb.200912087","volume":"190","author":"Z Kuang","year":"2010","unstructured":"Kuang, Z. et al. The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for proteasomal degradation. J. Cell Biol. 190, 129\u2013141 (2010).","journal-title":"J. Cell Biol."},{"key":"53006_CR34","doi-asserted-by":"publisher","first-page":"9009","DOI":"10.1074\/jbc.M110.190678","volume":"286","author":"T Nishiya","year":"2011","unstructured":"Nishiya, T. et al. Regulation of inducible nitric-oxide synthase by the SPRY domain- and SOCS box-containing proteins. J. Biol. Chem. 286, 9009\u20139019 (2011).","journal-title":"J. Biol. Chem."},{"key":"53006_CR35","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.cellsig.2014.02.011","volume":"26","author":"J Nicholson","year":"2014","unstructured":"Nicholson, J. et al. A systems-wide mass spectrometric-based linear motif screen to identify dominant in-vivo interacting proteins for the ubiquitin ligase MDM2. Cell Signal 26, 1243\u20131257 (2014).","journal-title":"Cell Signal"},{"key":"53006_CR36","volume":"9","author":"H Lin","year":"2022","unstructured":"Lin, H. et al. Hepatic MDM2 causes metabolic-associated fatty liver disease by blocking triglyceride-VLDL secretion via ApoB degradation. Adv. Sci. (Weinh.) 9, e2200742 (2022).","journal-title":"Adv. Sci. (Weinh.)"},{"key":"53006_CR37","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1128\/MMBR.05015-11","volume":"76","author":"JR Tisoncik","year":"2012","unstructured":"Tisoncik, J. R. et al. Into the eye of the cytokine storm. Microbiol Mol. Biol. Rev. 76, 16\u201332 (2012).","journal-title":"Microbiol Mol. Biol. Rev."},{"key":"53006_CR38","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.tim.2011.01.001","volume":"19","author":"L Dejager","year":"2011","unstructured":"Dejager, L., Pinheiro, I., Dejonckheere, E. & Libert, C. Cecal ligation and puncture: the gold standard model for polymicrobial sepsis? Trends Microbiol 19, 198\u2013208 (2011).","journal-title":"Trends Microbiol"},{"key":"53006_CR39","doi-asserted-by":"publisher","first-page":"3649","DOI":"10.2337\/db16-0012","volume":"65","author":"A Takikawa","year":"2016","unstructured":"Takikawa, A. et al. HIF-1alpha in myeloid cells promotes adipose tissue remodeling toward insulin resistance. Diabetes 65, 3649\u20133659 (2016).","journal-title":"Diabetes"},{"key":"53006_CR40","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1111\/imm.13002","volume":"155","author":"L Russo","year":"2018","unstructured":"Russo, L. & Lumeng, C. N. Properties and functions of adipose tissue macrophages in obesity. Immunology 155, 407\u2013417 (2018).","journal-title":"Immunology"},{"key":"53006_CR41","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.celrep.2019.06.018","volume":"28","author":"JD Bailey","year":"2019","unstructured":"Bailey, J. D. et al. Nitric oxide modulates metabolic remodeling in inflammatory macrophages through TCA cycle regulation and itaconate accumulation. Cell Rep. 28, 218\u2013230 e217 (2019).","journal-title":"Cell Rep."},{"key":"53006_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101354","volume":"28","author":"V Somasundaram","year":"2020","unstructured":"Somasundaram, V. et al. Inducible nitric oxide synthase-derived extracellular nitric oxide flux regulates proinflammatory responses at the single cell level. Redox Biol. 28, 101354 (2020).","journal-title":"Redox Biol."},{"key":"53006_CR43","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.2337\/db15-1624","volume":"65","author":"JE Jang","year":"2016","unstructured":"Jang, J. E. et al. Nitric oxide produced by macrophages inhibits adipocyte differentiation and promotes profibrogenic responses in preadipocytes to induce adipose tissue fibrosis. Diabetes 65, 2516\u20132528 (2016).","journal-title":"Diabetes"},{"key":"53006_CR44","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1210\/me.2009-0462","volume":"24","author":"M Lu","year":"2010","unstructured":"Lu, M. et al. Inducible nitric oxide synthase deficiency in myeloid cells does not prevent diet-induced insulin resistance. Mol. Endocrinol. 24, 1413\u20131422 (2010).","journal-title":"Mol. Endocrinol."},{"key":"53006_CR45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.niox.2010.04.007","volume":"23","author":"A Pautz","year":"2010","unstructured":"Pautz, A. et al. Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 23, 75\u201393 (2010).","journal-title":"Nitric Oxide"},{"key":"53006_CR46","doi-asserted-by":"publisher","first-page":"7516","DOI":"10.4049\/jimmunol.178.12.7516","volume":"178","author":"C Peyssonnaux","year":"2007","unstructured":"Peyssonnaux, C. et al. Cutting edge: essential role of hypoxia inducible factor-1alpha in development of lipopolysaccharide-induced sepsis. J. Immunol. 178, 7516\u20137519 (2007).","journal-title":"J. Immunol."},{"key":"53006_CR47","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1101\/gad.1881410","volume":"24","author":"N Takeda","year":"2010","unstructured":"Takeda, N. et al. Differential activation and antagonistic function of HIF-{alpha} isoforms in macrophages are essential for NO homeostasis. Genes Dev. 24, 491\u2013501 (2010).","journal-title":"Genes Dev."},{"key":"53006_CR48","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1172\/JCI23865","volume":"115","author":"C Peyssonnaux","year":"2005","unstructured":"Peyssonnaux, C. et al. HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J. Clin. Invest 115, 1806\u20131815 (2005).","journal-title":"J. Clin. Invest"},{"key":"53006_CR49","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.molmed.2018.10.006","volume":"25","author":"ER Watts","year":"2019","unstructured":"Watts, E. R. & Walmsley, S. R. Inflammation and Hypoxia: HIF and PHD Isoform Selectivity. Trends Mol. Med. 25, 33\u201346 (2019).","journal-title":"Trends Mol. Med"},{"key":"53006_CR50","doi-asserted-by":"publisher","first-page":"22785","DOI":"10.1074\/jbc.M114.587493","volume":"289","author":"S Joshi","year":"2014","unstructured":"Joshi, S., Singh, A. R. & Durden, D. L. MDM2 regulates hypoxic hypoxia-inducible factor 1alpha stability in an E3 ligase, proteasome, and PTEN-phosphatidylinositol 3-kinase-AKT-dependent manner. J. Biol. Chem. 289, 22785\u201322797 (2014).","journal-title":"J. Biol. Chem."},{"key":"53006_CR51","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/jcp.20406","volume":"204","author":"AL Nieminen","year":"2005","unstructured":"Nieminen, A. L., Qanungo, S., Schneider, E. A., Jiang, B. H. & Agani, F. H. Mdm2 and HIF-1alpha interaction in tumor cells during hypoxia. J. Cell Physiol. 204, 364\u2013369 (2005).","journal-title":"J. Cell Physiol."},{"key":"53006_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11740","volume":"7","author":"X Li","year":"2016","unstructured":"Li, X. et al. The MDM2-p53-pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic beta-cells. Nat. Commun. 7, 11740 (2016).","journal-title":"Nat. Commun."},{"key":"53006_CR53","doi-asserted-by":"publisher","first-page":"5063","DOI":"10.4049\/jimmunol.0803526","volume":"182","author":"G Liu","year":"2009","unstructured":"Liu, G., Park, Y. J., Tsuruta, Y., Lorne, E. & Abraham, E. p53 attenuates lipopolysaccharide-induced NF-kappaB activation and acute lung injury. J. Immunol. 182, 5063\u20135071 (2009).","journal-title":"J. Immunol."},{"key":"53006_CR54","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1073\/pnas.0237083100","volume":"100","author":"LJ Hofseth","year":"2003","unstructured":"Hofseth, L. J. et al. Nitric oxide-induced cellular stress and p53 activation in chronic inflammation. Proc. Natl Acad. Sci. USA 100, 143\u2013148 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"53006_CR55","doi-asserted-by":"publisher","first-page":"15697","DOI":"10.1074\/jbc.M112068200","volume":"277","author":"X Wang","year":"2002","unstructured":"Wang, X., Michael, D., de Murcia, G. & Oren, M. p53 activation by nitric oxide involves down-regulation of Mdm2. J. Biol. Chem. 277, 15697\u201315702 (2002).","journal-title":"J. Biol. Chem."},{"key":"53006_CR56","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1038\/sj.onc.1206431","volume":"22","author":"N Schneiderhan","year":"2003","unstructured":"Schneiderhan, N., Budde, A., Zhang, Y. & Brune, B. Nitric oxide induces phosphorylation of p53 and impairs nuclear export. Oncogene 22, 2857\u20132868 (2003).","journal-title":"Oncogene"},{"key":"53006_CR57","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.2337\/db18-0684","volume":"67","author":"Z Liu","year":"2018","unstructured":"Liu, Z. et al. The dysfunctional MDM2-p53 axis in adipocytes contributes to aging-related metabolic complications by induction of lipodystrophy. Diabetes 67, 2397\u20132409 (2018).","journal-title":"Diabetes"},{"key":"53006_CR58","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/gene.10066","volume":"32","author":"JD Grier","year":"2002","unstructured":"Grier, J. D., Yan, W. & Lozano, G. Conditional allele of mdm2 which encodes a p53 inhibitor. Genesis 32, 145\u2013147 (2002).","journal-title":"Genesis"},{"key":"53006_CR59","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1007\/s12016-017-8648-x","volume":"56","author":"S Jaillon","year":"2019","unstructured":"Jaillon, S., Berthenet, K. & Garlanda, C. Sexual dimorphism in innate immunity. Clin. Rev. Allergy Immunol. 56, 308\u2013321 (2019).","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"53006_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26987-1","volume":"12","author":"KKL Wu","year":"2021","unstructured":"Wu, K. K. L. et al. The APPL1-Rab5 axis restricts NLRP3 inflammasome activation through early endosomal-dependent mitophagy in macrophages. Nat. Commun. 12, 6637 (2021).","journal-title":"Nat. Commun."},{"key":"53006_CR61","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"53006_CR62","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923\u2013930 (2014).","journal-title":"Bioinformatics"},{"key":"53006_CR63","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"53006_CR64","doi-asserted-by":"publisher","first-page":"2791","DOI":"10.1194\/jlr.D023788","volume":"53","author":"M Galarraga","year":"2012","unstructured":"Galarraga, M. et al. Adiposoft: automated software for the analysis of white adipose tissue cellularity in histological sections. J. Lipid Res. 53, 2791\u20132796 (2012).","journal-title":"J. Lipid Res"},{"key":"53006_CR65","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1177\/0192623315625859","volume":"44","author":"SA Elmore","year":"2016","unstructured":"Elmore, S. A. et al. Recommendations from the INHAND apoptosis\/necrosis working group. Toxicol. Pathol. 44, 173\u2013188 (2016).","journal-title":"Toxicol. Pathol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-53006-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-53006-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-53006-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T18:02:21Z","timestamp":1728064941000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-53006-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,4]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["53006"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-53006-w","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,4]]},"assertion":[{"value":"20 October 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8624"}}