{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:28:46Z","timestamp":1790832526852,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]},{"name":"MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases","award":["CN_0000004"],"award-info":[{"award-number":["CN_0000004"]}]},{"name":"MUR PNRR National Center for Gene Therapy and Drugs based on RNA Technology","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]},{"name":"MUR PNRR National Center for Gene Therapy and Drugs based on RNA Technology","award":["CN_0000004"],"award-info":[{"award-number":["CN_0000004"]}]},{"name":"MIUR (Italian Ministry for Education, University and Research)","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]},{"name":"MIUR (Italian Ministry for Education, University and Research)","award":["CN_0000004"],"award-info":[{"award-number":["CN_0000004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups between acetyl-CoA and carnitine. This enzymatic activity ensures the optimal functioning of mitochondrial carbon flux by preventing acetyl-CoA accumulation, buffering metabolic flexibility, and regulating the balance between fatty acid and glucose oxidation. CRAT\u2019s interplay with the mitochondrial carnitine shuttle, involving carnitine palmitoyltransferases (CPT1 and CPT2) and the carnitine carrier (SLC25A20), underscores its critical role in energy metabolism. Emerging evidence highlights the structural and functional diversity of CRAT and structurally related acetyltransferases across cellular compartments, illustrating their coordinated role in lipid metabolism, amino acid catabolism, and mitochondrial bioenergetics. Moreover, the structural insights into CRAT have paved the way for understanding its regulation and identifying potential modulators with therapeutic applications for diseases such as diabetes, mitochondrial disorders, and cancer. This review examines CRAT\u2019s structural and functional aspects, its relationships with carnitine shuttle members and other carnitine acyltransferases, and its broader role in metabolic health and disease. The potential for targeting CRAT and its associated pathways offers promising avenues for therapeutic interventions aimed at restoring metabolic equilibrium and addressing metabolic dysfunction in disease states.<\/jats:p>","DOI":"10.3390\/biom15020216","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:36:32Z","timestamp":1738560992000},"page":"216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Carnitine O-Acetyltransferase as a Central Player in Lipid and Branched-Chain Amino Acid Metabolism, Epigenetics, Cell Plasticity, and Organelle Function"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8047-3881","authenticated-orcid":false,"given":"Mariateresa","family":"Volpicella","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d; Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6916-325X","authenticated-orcid":false,"given":"Maria Noemi","family":"Sgobba","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d; Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5266-1156","authenticated-orcid":false,"given":"Luna","family":"Laera","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d; Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8947-9733","authenticated-orcid":false,"given":"Anna Lucia","family":"Francavilla","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d; Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danila Imperia","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d; Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-9405","authenticated-orcid":false,"given":"Lorenzo","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d; Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1816-548X","authenticated-orcid":false,"given":"Ciro Leonardo","family":"Pierri","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Structural and Molecular Biology, Department of Pharmacy\u2014Pharmaceutical Sciences, University of Bari \u201cAldo Moro\u201d, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-4263","authenticated-orcid":false,"given":"Anna","family":"De Grassi","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment, University of Bari \u201cAldo Moro\u201d; Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/humu.23901","article-title":"CRAT missense variants cause abnormal carnitine acetyltransferase function in an early-onset case of Leigh syndrome","volume":"41","author":"Laera","year":"2020","journal-title":"Hum. 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