{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:27:19Z","timestamp":1790512039201,"version":"4.1.0"},"reference-count":97,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["TU492\/3-1"],"award-info":[{"award-number":["TU492\/3-1"]}]},{"name":"Fritz-Thyssen-Stiftung","award":["Az.10.15.2.039MN"],"award-info":[{"award-number":["Az.10.15.2.039MN"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In general, metabolic flexibility refers to an organism\u2019s capacity to adapt to metabolic changes due to differing energy demands. The aim of this work is to summarize and discuss recent findings regarding variables that modulate energy regulation in two different pathways of mitochondrial fatty metabolism: \u03b2-oxidation and fatty acid biosynthesis. We focus specifically on two diseases: very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and malonyl-CoA synthetase deficiency (acyl-CoA synthetase family member 3 (ACSF3)) deficiency, which are both characterized by alterations in metabolic flexibility. On the one hand, in a mouse model of VLCAD-deficient (VLCAD\u2212\/\u2212) mice, the white skeletal muscle undergoes metabolic and morphologic transdifferentiation towards glycolytic muscle fiber types via the up-regulation of mitochondrial fatty acid biosynthesis (mtFAS). On the other hand, in ACSF3-deficient patients, fibroblasts show impaired mitochondrial respiration, reduced lipoylation, and reduced glycolytic flux, which are compensated for by an increased \u03b2-oxidation rate and the use of anaplerotic amino acids to address the energy needs. Here, we discuss a possible co-regulation by mtFAS and \u03b2-oxidation in the maintenance of energy homeostasis.<\/jats:p>","DOI":"10.3390\/ijms22073799","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T21:44:47Z","timestamp":1617745487000},"page":"3799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Altered Metabolic Flexibility in Inherited Metabolic Diseases of Mitochondrial Fatty Acid Metabolism"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3851-4843","authenticated-orcid":false,"given":"Sara","family":"Tucci","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center-University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-0092","authenticated-orcid":false,"given":"Khaled Ibrahim","family":"Alatibi","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center-University of Freiburg, 79106 Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, Schaenzlestrasse 1, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7253-2765","authenticated-orcid":false,"given":"Zeinab","family":"Wehbe","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center-University of Freiburg, 79106 Freiburg, Germany"},{"name":"Center of Pediatric and Adolescent Medicine-Medical Center, Department of Pediatric Hematology and Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/ncb3124","article-title":"Metabolic pathways promoting cancer cell survival and growth","volume":"17","author":"Boroughs","year":"2015","journal-title":"Nat. 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