{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T02:02:40Z","timestamp":1775872960644,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2018YFD0900400"],"award-info":[{"award-number":["2018YFD0900400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Scientific Foundation of China","award":["32002365"],"award-info":[{"award-number":["32002365"]}]},{"name":"Shandong Natural Scientific Foundation","award":["ZR2020QC204"],"award-info":[{"award-number":["ZR2020QC204"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M660169"],"award-info":[{"award-number":["2019M660169"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Aoshan Talents Cultivation Program supported by Qingdao National Laboratory for Marine Science and Technology","award":["2017ASTCP-OS12"],"award-info":[{"award-number":["2017ASTCP-OS12"]}]},{"name":"Key R&amp;D Program in Shandong Province","award":["2020ZLYS03"],"award-info":[{"award-number":["2020ZLYS03"]}]},{"name":"China Agriculture Research System","award":["CARS-47-G10"],"award-info":[{"award-number":["CARS-47-G10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Eukaryotic cells control nutritional homeostasis and determine cell metabolic fate through a series of nutrient transporters and metabolic regulation pathways. Lysosomal localized amino acid transporter member 9 of the solute carrier family 38 (SLC38A9) regulates essential amino acids\u2019 efflux from lysosomes in an arginine-regulated fashion. To better understand the physiological role of SLC38A9, we first described the spatiotemporal expression pattern of the slc38a9 gene in zebrafish. A quarter of slc38a9\u2212\/\u2212 mutant embryos developed pericardial edema and died prematurely, while the remaining mutants were viable and grew normally. By profiling the transcriptome of the abnormally developed embryos using RNA-seq, we identified increased apoptosis, dysregulated amino acid metabolism, and glycolysis\/gluconeogenesis disorders that occurred in slc38a9\u2212\/\u2212 mutant fish. slc38a9 deficiency increased whole-body free amino acid and lactate levels but reduced glucose and pyruvate levels. The change of glycolysis-related metabolites in viable slc38a9\u2212\/\u2212 mutant fish was ameliorated. Moreover, loss of slc38a9 resulted in a significant reduction in hypoxia-inducible gene expression and hypoxia-inducible factor 1-alpha (Hif1\u03b1) protein levels. These results improved our understanding of the physiological functions of SLC38A9 and revealed its indispensable role in embryonic development, metabolic regulation, and stress adaption.<\/jats:p>","DOI":"10.3390\/ijms23084200","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:23:11Z","timestamp":1649722991000},"page":"4200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Slc38a9 Deficiency Induces Apoptosis and Metabolic Dysregulation and Leads to Premature Death in Zebrafish"],"prefix":"10.3390","volume":"23","author":[{"given":"Xiya","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengdong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huihui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kangsen","family":"Mai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture, Ocean University of China, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Aquaculture Nutrition and Feeds, Ministry of Agriculture, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.domaniend.2014.10.003","article-title":"Impact of maternal malnutrition during the periconceptional period on mammalian preimplantation embryo development","volume":"51","author":"Velazquez","year":"2015","journal-title":"Domest. 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