{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:19Z","timestamp":1792789639584,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Christian Doppler Laboratory for Iron Metabolism and Anemia Research","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"FWF funded doctoral program HOROS","award":["W-1253"],"award-info":[{"award-number":["W-1253"]}]},{"name":"transnational doctoral program BI-DOC","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Iron is an essential component for metabolic processes, including oxygen transport within hemoglobin, tricarboxylic acid (TCA) cycle activity, and mitochondrial energy transformation. Iron deficiency can thus lead to metabolic dysfunction and eventually result in iron deficiency anemia (IDA), which affects approximately 1.5 billion people worldwide. Using a rat model of IDA induced by phlebotomy, we studied the effects of IDA on mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and the liver. Furthermore, we evaluated whether the mitochondrial function evaluated by high-resolution respirometry in PBMCs reflects corresponding alterations in the liver. Surprisingly, mitochondrial respiratory capacity was increased in PBMCs from rats with IDA compared to the controls. In contrast, mitochondrial respiration remained unaffected in livers from IDA rats. Of note, citrate synthase activity indicated an increased mitochondrial density in PBMCs, whereas it remained unchanged in the liver, partly explaining the different responses of mitochondrial respiration in PBMCs and the liver. Taken together, these results indicate that mitochondrial function determined in PBMCs cannot serve as a valid surrogate for respiration in the liver. Metabolic adaptions to iron deficiency resulted in different metabolic reprogramming in the blood cells and liver tissue.<\/jats:p>","DOI":"10.3390\/metabo12030270","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T21:48:42Z","timestamp":1647899322000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mitochondrial Respiration in Response to Iron Deficiency Anemia: Comparison of Peripheral Blood Mononuclear Cells and Liver"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-5030","authenticated-orcid":false,"given":"Christine","family":"Fischer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Valente de Souza","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9876-1411","authenticated-orcid":false,"given":"Timea","family":"Koml\u00f3di","sequence":"additional","affiliation":[{"name":"Oroboros Instruments, Sch\u00f6pfstrasse 18, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1474-5428","authenticated-orcid":false,"given":"Luiz F.","family":"Garcia-Souza","sequence":"additional","affiliation":[{"name":"Oroboros Instruments, Sch\u00f6pfstrasse 18, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Volani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Tymoszuk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egon","family":"Demetz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Auer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hilbe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Brigo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Petzer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Asshoff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3647-5895","authenticated-orcid":false,"given":"Erich","family":"Gnaiger","sequence":"additional","affiliation":[{"name":"Oroboros Instruments, Sch\u00f6pfstrasse 18, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0709-2158","authenticated-orcid":false,"given":"G\u00fcnter","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"},{"name":"Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1056\/NEJMra1401038","article-title":"Iron-Deficiency Anemia","volume":"372","author":"Camaschella","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.hoc.2015.11.002","article-title":"The Global Burden of Anemia","volume":"30","author":"Kassebaum","year":"2016","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lanser, L., Burkert, F.R., Bellmann-Weiler, R., Schroll, A., Wildner, S., Fritsche, G., and Weiss, G. (2021). Dynamics in Anemia Development and Dysregulation of Iron Homeostasis in Hospitalized Patients with COVID-19. Metabolites, 11.","DOI":"10.3390\/metabo11100653"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1079\/PHN2004677","article-title":"Effect of iron supplementation on mental and motor development in children: Systematic review of randomised controlled trials","volume":"8","author":"Sachdev","year":"2005","journal-title":"Public Health Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0140-6736(20)32594-0","article-title":"Iron deficiency","volume":"397","author":"Pasricha","year":"2021","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2016.12.034","article-title":"A Red Carpet for Iron Metabolism","volume":"168","author":"Muckenthaler","year":"2017","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100866","DOI":"10.1016\/j.mam.2020.100866","article-title":"Basics and principles of cellular and systemic iron homeostasis","volume":"75","author":"Katsarou","year":"2020","journal-title":"Mol. Asp. Med."},{"key":"ref_8","first-page":"112","article-title":"Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed","volume":"2020","author":"Gnaiger","year":"2020","journal-title":"Bioenerg. Commun."},{"key":"ref_9","first-page":"1","article-title":"MitoEAGLE Task Group. Mitochondrial physiology","volume":"2020","author":"Gnaiger","year":"2020","journal-title":"Bioenerg. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/nature08301","article-title":"Function and biogenesis of iron\u2013sulphur proteins","volume":"460","author":"Lill","year":"2009","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0005-2728(99)00088-2","article-title":"Iron-dependent changes in cellular energy metabolism: Influence on citric acid cycle and oxidative phosphorylation","volume":"1413","author":"Oexle","year":"1999","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1042\/BJ20101825","article-title":"Regulation of cellular iron metabolism","volume":"434","author":"Wang","year":"2011","journal-title":"Biochem. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nemeth, E., and Ganz, T. (2021). Hepcidin-Ferroportin Interaction Controls Systemic Iron Homeostasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126493"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0005-2728(87)90001-6","article-title":"Substrate-dependent functional defects and altered mitochondrial respiratory capacity in hearts from guinea pigs with iron deficiency anemia","volume":"891","author":"Macdonald","year":"1987","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1002\/ejhf.1154","article-title":"Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function","volume":"20","author":"Hoes","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13827","DOI":"10.1016\/S0021-9258(18)67094-2","article-title":"Perturbation of mitochondrial composition in muscle by iron deficiency. Implications regarding regulation of mitochondrial assembly","volume":"261","author":"Cartier","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ijcard.2018.02.021","article-title":"Iron deficiency without anemia is responsible for decreased left ventricular function and reduced mitochondrial complex I activity in a mouse model","volume":"266","author":"Rineau","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/0304-4165(83)90061-2","article-title":"and Brown, E.B. Tissue effects of iron deficiency in the rat","volume":"757","author":"McKay","year":"1983","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1182\/blood.V35.4.496.496","article-title":"Enlargement of Mitochondrial Compartment in Iron and Copper Deficiency","volume":"35","author":"Dallman","year":"1970","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1083\/jcb.48.1.79","article-title":"The effects of iron deficiency on the hepatocyte: A biochemical and ultrastructural study","volume":"48","author":"Dallman","year":"1971","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/mds.27482","article-title":"Association of mitochondrial iron deficiency and dysfunction with idiopathic restless legs syndrome","volume":"34","author":"Haschka","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.mito.2020.12.010","article-title":"Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (NAFLD)","volume":"57","author":"Ajaz","year":"2021","journal-title":"Mitochondrion"},{"key":"ref_23","first-page":"2702","article-title":"Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis","volume":"35","author":"Belikova","year":"2007","journal-title":"Crit. Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1097\/CCM.0b013e31820eda5c","article-title":"Bioenergetic failure of human peripheral blood monocytes in patients with septic shock is mediated by reduced F1Fo adenosine-5\u2032-triphosphate synthase activity","volume":"39","author":"Santiago","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.1182\/blood-2008-12-195651","article-title":"Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: Diagnostic and therapeutic implications","volume":"113","author":"Theurl","year":"2009","journal-title":"Blood"},{"key":"ref_26","unstructured":"Palmeira, C.M., and Moreno, A.J. (2018). High-Resolution FluoRespirometry and OXPHOS Protocols for Human Cells, Permeabilized Fibers from Small Biopsies of Muscle, and Isolated Mitochondria. Mitochondrial Bioenergetics: Methods and Protocols, Springer."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1039\/C7MT00177K","article-title":"Dietary iron loading negatively affects liver mitochondrial function","volume":"9","author":"Volani","year":"2017","journal-title":"Metallomics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/0006-291X(70)90017-3","article-title":"Mitochondrial citric acid cycle and related enzymes: Adaptive response to exercise","volume":"40","author":"Holloszy","year":"1970","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1432-1033.1989.tb14551.x","article-title":"Chronic stimulation of rat skeletal muscle induces coordinate increases in mitochondrial and nuclear mRNAs of cytochrome-c-oxidase subunits","volume":"179","author":"Hood","year":"1989","journal-title":"Eur. J. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0021-9258(17)42482-3","article-title":"Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle","volume":"261","author":"Williams","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/sms.12612","article-title":"Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and Caucasians in the arctic winter","volume":"25","author":"Gnaiger","year":"2015","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1111\/trf.13588","article-title":"Blood removal therapy in hereditary hemochromatosis induces a stress response resulting in improved genome integrity","volume":"56","author":"Distante","year":"2016","journal-title":"Transfusion"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1136\/jcp.27.12.973","article-title":"Morphological abnormalities in lymphocyte mitochondria associated with iron-deficiency anaemia","volume":"27","author":"Jarvis","year":"1974","journal-title":"J. Clin. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.3324\/haematol.2011.048926","article-title":"Pathways for the regulation of hepcidin expression in anemia of chronic disease and iron deficiency anemia in vivo","volume":"96","author":"Theurl","year":"2011","journal-title":"Haematologica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41556-021-00837-0","article-title":"Metabolic determination of cell fate through selective inheritance of mitochondria","volume":"24","author":"Kuuluvainen","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fischer, C., Volani, C., Koml\u00f3di, T., Seifert, M., Demetz, E., Valente de Souza, L., Auer, K., Petzer, V., von Raffay, L., and Moser, P. (2021). Dietary Iron Overload and Hfe\u2212\/\u2212 Related Hemochromatosis Alter Hepatic Mitochondrial Function. Antioxidants, 10.","DOI":"10.3390\/antiox10111818"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Volani, C., Paglia, G., Smarason, S.V., Pramstaller, P.P., Demetz, E., Pfeifhofer-Obermair, C., and Weiss, G. (2018). Metabolic Signature of Dietary Iron Overload in a Mouse Model. Cells, 7.","DOI":"10.3390\/cells7120264"},{"key":"ref_38","unstructured":"(2022, February 23). SUIT-001 O2 ce-pce D003. Available online: https:\/\/www.bioblast.at\/index.php\/SUIT-001_O2_ce-pce_D003."},{"key":"ref_39","unstructured":"(2022, February 23). SUIT-001 O2 mt D001. Available online: https:\/\/www.bioblast.at\/index.php\/SUIT-001_O2_mt_D001."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/j.jnutbio.2011.10.013","article-title":"High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption","volume":"23","author":"Sonnweber","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Brigo, N., Pfeifhofer-Obermair, C., Tymoszuk, P., Demetz, E., Engl, S., Barros-Pinkelnig, M., Dichtl, S., Fischer, C., De Souza, V.L., and Petzer, V. (2021). Cytokine-Mediated Regulation of ARG1 in Macrophages and Its Impact on the Control of Salmonella enterica Serovar Typhimurium Infection. Cells, 10.","DOI":"10.3390\/cells10071823"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/3\/270\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:40:27Z","timestamp":1760136027000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/3\/270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,21]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["metabo12030270"],"URL":"https:\/\/doi.org\/10.3390\/metabo12030270","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,21]]}}}