{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:39:54Z","timestamp":1790354394714,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Mitochondrial trifunctional protein (TFP) deficiency is an inherited disorder of long\u2010chain fatty acid \u03b2\u2010oxidation (FAO). TFP is a heteromeric enzyme composed of two \u03b1 and two \u03b2\u2010subunits. Despite early detection and dietary treatment, TFP deficiency patients often develop hypoglycemia, rhabdomyolysis, cardiomyopathy, and peripheral neuropathy. Degenerative retinopathy and milder peripheral neuropathy occur in patients with an isolated deficiency of the \u03b1TFP subunit of long\u2010chain 3\u2010hydroxyacyl\u2010CoA dehydrogenase (LCHAD) activity. Triheptanoin treatment improves most complications, but not peripheral neuropathy and retinopathy. Notably, TFP also carries a fourth enzymatic function involved in cardiolipin remodeling, which we previously found to be impaired in TFP\/LCHAD deficiency. We therefore tested whether elamipretide, a synthetic cardiolipin\u2010binding peptide, could improve mitochondrial function and cardiolipin levels in \u03b2TFP\u2010deficient mice and patient\u2010derived fibroblasts. Mice were treated with elamipretide delivered by osmotic minipump and challenged with treadmill exercise or cold stress after fasting. \u03b2TFP\u2010deficient mice treated with elamipretide showed improved exercise endurance, but cold tolerance was not altered. Liver mitochondria from male \u03b2TFP\u2010deficient mice demonstrated improved FAO\u2010ETC enzyme activities. However, cardiolipin content and composition were unchanged. In patient fibroblasts, elamipretide produced a possible genotype\u2010dependent increase in mitochondrial bioenergetics and a reduction in ROS. These results support a mechanism in which elamipretide stabilizes between FAO enzymes and ETC complexes, thereby improving mitochondrial function independently of changes in cardiolipin levels. Elamipretide thus emerges as a potential therapeutic agent for TFP\/LCHAD deficiency, warranting further preclinical studies.<\/jats:p>","DOI":"10.1002\/jimd.70132","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T02:30:33Z","timestamp":1767839433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Elamipretide Improves Mitochondrial Function in Mitochondrial Trifunctional Protein\u2010Deficient Mice and Human Fibroblasts"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0247-837X","authenticated-orcid":false,"given":"Eduardo","family":"Vieira Neto","sequence":"first","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Pediatrics Children's Neuroscience Institute, School of Medicine, University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meicheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Genetic and Genomic Medicine Division, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin J.","family":"Szuminsky","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Kenneth P. 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