{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:55:58Z","timestamp":1792799758818,"version":"4.5.0"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":615,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Pittsburgh Children\u2019s Neuroscience Institute","award":["2022\/2023 INA Grant Award"],"award-info":[{"award-number":["2022\/2023 INA Grant Award"]}],"id":[{"id":"https:\/\/ror.org\/0240rwx68","id-type":"ROR","asserted-by":"crossref"}]},{"name":"UPMC Children\u2019s Hospital of Pittsburgh Foundation","award":["Matthew Fisch Fund"],"award-info":[{"award-number":["Matthew Fisch Fund"]}],"id":[{"id":"https:\/\/ror.org\/03763ep67","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NS061817"],"award-info":[{"award-number":["NS061817"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA243142"],"award-info":[{"award-number":["CA243142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL174611"],"award-info":[{"award-number":["HL174611"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,10]]},"abstract":"<jats:p>\n                    Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder leading to a block in long-chain fatty acid \u03b2-oxidation. Mutations in\n                    <jats:italic>HADHA<\/jats:italic>\n                    and\n                    <jats:italic>HADHB<\/jats:italic>\n                    , which encode the TFP \u03b1 and \u03b2 subunits, respectively, usually result in combined TFP deficiency. A single common mutation,\n                    <jats:italic>HADHA<\/jats:italic>\n                    c.1528G&gt;C (p.E510Q), leads to isolated 3-hydroxyacyl-CoA dehydrogenase deficiency. TFP also catalyzes a step in the remodeling of cardiolipin (CL), a phospholipid critical to mitochondrial membrane stability and function. We explored the effect of mutations in TFP subunits on CL and other phospholipid content and composition and the consequences of these changes on mitochondrial bioenergetics in patient-derived fibroblasts. Abnormalities in these parameters varied extensively among different fibroblasts, and some cells were able to maintain basal oxygen consumption rates similar to controls. Although CL reduction was universally identified, a simultaneous increase in monolysocardiolipins was discrepant among cells. A similar profile was seen in liver mitochondria isolates from a TFP-deficient mouse model. Response to new potential drugs targeting CL metabolism might be dependent on patient genotype.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.176887","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T12:02:42Z","timestamp":1722513762000},"source":"Crossref","is-referenced-by-count":19,"title":["Mitochondrial bioenergetics and cardiolipin remodeling abnormalities in mitochondrial trifunctional protein deficiency"],"prefix":"10.1172","volume":"9","author":[{"given":"Eduardo","family":"Vieira Neto","sequence":"first","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh,"},{"name":"Children\u2019s Neuroscience Institute, Department of Pediatrics, School of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meicheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin J.","family":"Szuminsky","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Kenneth P. Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lethicia","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh,"},{"name":"School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4175-7777","authenticated-orcid":true,"given":"Erik","family":"Koppes","sequence":"additional","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudong","family":"Wang","sequence":"additional","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clinton","family":"Van\u2019t Land","sequence":"additional","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Al-Walid","family":"Mohsen","sequence":"additional","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geancarlo","family":"Zanatta","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areeg H.","family":"El-Gharbawy","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3460-5003","authenticated-orcid":true,"given":"Tamil S.","family":"Anthonymuthu","sequence":"additional","affiliation":[{"name":"Adeptrix Corporation, Beverly, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia Y.","family":"Tyurina","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, School of Public Health;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3474-1697","authenticated-orcid":true,"given":"Vladimir A.","family":"Tyurin","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, School of Public Health;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7245-1885","authenticated-orcid":true,"given":"Valerian","family":"Kagan","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, School of Public Health;"},{"name":"Department of Pharmacology and Chemical Biology, School of Medicine; Department of Chemistry, Kenneth P. Dietrich School of Arts and Sciences; and Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fclya","family":"Bayir","sequence":"additional","affiliation":[{"name":"Division of Critical Care and Hospital Medicine, Department of Pediatrics, Redox Health Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-6457","authenticated-orcid":true,"given":"Jerry","family":"Vockley","sequence":"additional","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children\u2019s Hospital of Pittsburgh,"},{"name":"Department of Human Genetics, School of Public Health, Center for Rare Disease Therapy, UPMC Children\u2019s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.10.57"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.3.022502.103213"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9090-x"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9076-8"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.02.015"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105045"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2018.02.009"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1801252115"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816317116"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.04.006"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118863"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.1.99"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02199-3"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048628"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.048322"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2016.08.001"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12461"},{"key":"B18","article-title":"Barth Syndrome: from mitochondrial dysfunctions associated with aberrant production of reactive oxygen species to pluripotent stem cell studies","volume":"6","author":"Saric","year":"2015","journal-title":"Front Genet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307382200"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-014-9591-7"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2018.04.001"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.07.003"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9188-1"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2017.52"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.06.011"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s40142-017-0125-6"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S171481"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.139493"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.008680"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000103931.80055.06"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-0533-8"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12482-1"},{"key":"B33","unstructured":"Lomb\u00e8s A, Thorburn DR. Laboratory diagnosis of mitochondrial diseases. In: Valle DL, et al., eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019. https:\/\/ommbid.mhmedical.com\/content.aspx?bookid=2709&sectionid=225089016"},{"key":"B34","unstructured":"DiMauro S, et al. Clinical diagnostic and therapeutic approach to the patient with suspected mitochondrial disease. In: Valle DL, et al., eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019. https:\/\/ommbid.mhmedical.com\/content.aspx?bookid=2709&sectionid=225890259"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20150648"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/47.7.1190"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051239"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101923"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy403"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101628R"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27206988"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/srep43878"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-020-04021-0"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2021.07.003"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102774"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114444"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2020.101068"},{"key":"B48"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213933"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.10.014"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1304"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-01006-8"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10211"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl433"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19543-3"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12492"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-134"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.01.005"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00926-4"},{"key":"B62","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0091-679X(06)80009-9","article-title":"Assays of fatty acid beta-oxidation activity","volume":"80","author":"Bennett","year":"2007","journal-title":"Methods Cell Biol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005694712583"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(02)00296-2"},{"key":"B65","first-page":"Unit 17.8.1","article-title":"Acylcarnitine analysis by tandem mass spectrometry","volume":"Chapter 17","author":"Smith","year":"2010","journal-title":"Curr Protoc Hum Genet"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.97677"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21168"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3195"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000003636"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D700041-JLR200"},{"key":"B72"},{"key":"B73","unstructured":"NIH. trifunctional enzyme subunit beta, mitochondrial isoform 1 precursor [Homo sapiens]. https:\/\/www.ncbi.nlm.nih.gov\/protein\/NP_000174.1 Updated April 4, 2024. Accessed June 13, 2023"},{"key":"B74","unstructured":"NIH. trifunctional enzyme subunit alpha, mitochondrial precursor [Homo sapiens]. https:\/\/www.ncbi.nlm.nih.gov\/protein\/NP_000173.2 Updated July 27, 2024. Accessed June 13, 2023"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/176887\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:41:31Z","timestamp":1779136891000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/176887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,1]]},"references-count":74,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9,10]]},"published-print":{"date-parts":[[2024,9,10]]}},"alternative-id":["10.1172\/jci.insight.176887"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.176887","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,1]]},"article-number":"e176887"}}