{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:47:56Z","timestamp":1787726876886,"version":"build-2784847793"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Letters"],"abstract":"<jats:p>\n                    Lipoic acid is an essential cofactor for mitochondrial multienzyme complexes involved in central metabolism. In humans, mutations in the lipoyl transferase\n                    <jats:italic>LIPT2<\/jats:italic>\n                    impair mitochondrial protein lipoylation and cause severe metabolic disease. Here, we investigated the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    homolog,\n                    <jats:italic>lipT2<\/jats:italic>\n                    ,\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                    <jats:italic>lipT2<\/jats:italic>\n                    mutants exhibited locomotor defects and shortened lifespan, accompanied by markedly reduced lipoylation of pyruvate dehydrogenase (PDH) and 2\u2010oxoglutarate dehydrogenase (OGDH). Loss of\n                    <jats:italic>lipT2<\/jats:italic>\n                    impaired glucose oxidation and disrupted tricarboxylic acid (TCA) cycle activity, leading to reduced mitochondrial energy production. Metabolomic analysis revealed altered amino acid homeostasis, including a marked reduction in aspartate, a key TCA cycle\u2010derived metabolite. These findings demonstrate that defective lipoylation disrupts central metabolic processes and energy homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70422","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:30:26Z","timestamp":1785389426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of\n                    <scp>LipT2<\/scp>\n                    disrupts mitochondrial protein lipoylation and metabolic homeostasis in\n                    <i>Drosophila melanogaster<\/i>"],"prefix":"10.1002","author":[{"given":"Yoshihito","family":"Kishita","sequence":"first","affiliation":[{"name":"Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine Juntendo University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-9644","authenticated-orcid":false,"given":"Manabu","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Liberal Arts and Human Development Kanagawa University of Human Services  Yokosuka\u2010shi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Sato\u2010Miyata","sequence":"additional","affiliation":[{"name":"Research and Education Center for Natural Sciences Keio University  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Takeo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Laboratory of Cellular Genetics Tokyo Metropolitan University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-3109","authenticated-orcid":false,"given":"Toshiro","family":"Aigaki","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Laboratory of Cellular Genetics Tokyo Metropolitan University  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"8971","DOI":"10.1016\/S0021-9258(19)38795-2","article-title":"Structure\u2010function relationships in dihydrolipoamide acyltransferases","volume":"265","author":"Reed LJ","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/bj2570625","article-title":"The 2\u2010oxo acid dehydrogenase complexes: recent advances","volume":"257","author":"Yeaman SJ","year":"1989","journal-title":"Biochem 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oxidative stress in neurodegeneration","volume":"31","author":"Gibson GE","year":"2005","journal-title":"Mol Neurobiol"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.ajhg.2011.11.011","article-title":"Lipoic acid synthetase deficiency causes neonatal\u2010onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation","volume":"89","author":"Mayr JA","year":"2011","journal-title":"Am J Hum Genet"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13036-019-0164-5","article-title":"Quantitative study of H protein lipoylation of the glycine cleavage system and a strategy to increase its activity by co\u2010expression of LplA","volume":"13","author":"Zhang X","year":"2019","journal-title":"J Biol Eng"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1172\/JCI115209","article-title":"Maple syrup urine disease. Complete defect of the E1 beta subunit of the branched chain alpha\u2010ketoacid dehydrogenase complex due to a deletion of an 11\u2010bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the disease","volume":"87","author":"Nobukuni Y","year":"1991","journal-title":"J Clin Invest"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/jb.177.1.1-10.1995","article-title":"Lipoic acid metabolism in Escherichia coli: the lplA and lipB genes define redundant pathways for ligation of lipoyl groups to apoprotein","volume":"177","author":"Morris TW","year":"1995","journal-title":"J Bacteriol"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0076-6879(97)79021-9","article-title":"Biosynthesis of lipoic acid and posttranslational modification with lipoic acid in Escherichia coli","volume":"279","author":"Jordan SW","year":"1997","journal-title":"Methods 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RM","year":"2004","journal-title":"Biochemistry"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"15166","DOI":"10.1021\/bi002060n","article-title":"Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl\u2010acyl carrier protein","volume":"39","author":"Miller JR","year":"2000","journal-title":"Biochemistry"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.2337\/db08-0473","article-title":"Lipoic acid synthase (LASY): a novel role in inflammation, mitochondrial function, and insulin resistance","volume":"58","author":"Padmalayam I","year":"2009","journal-title":"Diabetes"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"8387","DOI":"10.1128\/MCB.25.18.8387-8392.2005","article-title":"Endogenous production of lipoic acid is essential for mouse development","volume":"25","author":"Yi X","year":"2005","journal-title":"Mol Cell 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