{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:04:35Z","timestamp":1789603475249,"version":"build-2803163510"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100025294","name":"Research Ireland","doi-asserted-by":"publisher","award":["15\/CDA\/3490"],"award-info":[{"award-number":["15\/CDA\/3490"]}],"id":[{"id":"10.13039\/501100025294","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Carbon dioxide (CO\n                    <jats:sub>2<\/jats:sub>\n                    ) is an ancient and ubiquitous physiological gas generated during aerobic respiration. Historically viewed as a simple metabolic waste product, CO\n                    <jats:sub>2<\/jats:sub>\n                    has received far less research attention than oxygen (O\n                    <jats:sub>2<\/jats:sub>\n                    ), the primary substrate of aerobic respiration. However, emerging evidence has revealed important roles for CO\n                    <jats:sub>2<\/jats:sub>\n                    in immunometabolism, immunology, muscle physiology, and clinical medicine. While circulating pCO\n                    <jats:sub>2<\/jats:sub>\n                    levels are tightly regulated, patients with lung diseases such as chronic obstructive pulmonary disease (COPD) frequently develop hypercapnia, pCO\n                    <jats:sub>2<\/jats:sub>\n                    &gt;\u200945\u2009mmHg. Hypercapnia is associated with significantly increased mortality, higher risk of ICU admission, and a global prevalence estimated at 13\u201315 million patients. Its broader clinical consequences remain poorly understood and are inadequately integrated into current therapeutic paradigms. Here, we examined the impact of hypercapnia on the metabolic profile of monocytes. We demonstrate that 24\u2009h of buffered hypercapnia induces a marked reduction in mitochondrial mass. This is accompanied by dysregulation of mitochondrial membrane potential and key bioenergetic substrates (NADH\/NAD\n                    <jats:sup>+<\/jats:sup>\n                    and ATP content). We further show that hypercapnia alters the abundance of metabolites and proteins associated with mitochondrial metabolism, with effects spanning glucose, glutamine, and lipid metabolism. Thus, we provide direct mechanistic evidence that hypercapnia directly alters the glutamine\u2013glutamate\u2013proline synthesis axis. Collectively, these findings establish the foundation for a discrete hypercapnic metabolic phenotype, that is, in several respects, distinct from the metabolic adaptations observed in hypoxia. We propose that hypercapnia triggers a cascade of metabolic adaptations with tissue\u2010dependent consequences on cellular effector functions.\n                  <\/jats:p>","DOI":"10.1111\/imcb.70162","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:50:32Z","timestamp":1789602632000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypercapnia Induces Mitochondrial Adaptations and Alters Glutamine Metabolism to Drive a Distinct Metabolic Phenotype in Monocytes"],"prefix":"10.1111","author":[{"given":"Ben","family":"Reddan","sequence":"first","affiliation":[{"name":"School of Medicine University College Dublin  Dublin Ireland"},{"name":"Conway Institute of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6156-9159","authenticated-orcid":false,"given":"David E.","family":"Phelan","sequence":"additional","affiliation":[{"name":"School of Medicine University College Dublin  Dublin Ireland"},{"name":"Conway Institute of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Yin","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"},{"name":"School of Agriculture and Food Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7711-7499","authenticated-orcid":false,"given":"Lorraine","family":"Brennan","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"},{"name":"School of Agriculture and Food Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Wallace","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"},{"name":"School of Agriculture and Food Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-8299","authenticated-orcid":false,"given":"Eoin P.","family":"Cummins","sequence":"additional","affiliation":[{"name":"School of Medicine University College Dublin  Dublin Ireland"},{"name":"Conway Institute of Biomolecular and Biomedical Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"StatPearls","author":"Pahal P.","year":"2025"},{"issue":"9","key":"e_1_2_11_3_1","first-page":"2005","article-title":"The pK of Specific Groups of Proteins. 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B.","year":"2010","journal-title":"Journal of Applied Physiology"},{"issue":"12","key":"e_1_2_11_36_1","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/labinvest.2013.118","article-title":"Hypercapnic Acidosis Confers Antioxidant and Anti\u2010Apoptosis Effects Against Ventilator\u2010Induced Lung Injury","volume":"93","author":"Yang W. 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