{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:06:30Z","timestamp":1790841990009,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T00:00:00Z","timestamp":1561334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700134"],"award-info":[{"award-number":["81700134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Acute myeloid leukaemia (AML) cells possess metabolism profiles, such as higher rates of oxidative phosphorylation and dependence on fatty acid oxidation for survival, and are dependent on the sophisticated regulation of reactive oxygen species (ROS) generation for survival, drug resistance and stemness maintenance. We found that sensitivity of primary AML cells to cytarabine correlated with SOD2 acetylation and the ability of the drug to induce mitochondrial ROS. The SOD2 deacetylase, SIRT3, protected AML cells from chemotherapy as shown by inhibited apoptosis via inhibited drug\u2010induced production of mitochondrial ROS. SIRT3 significantly decreased nicotinamide adenine dinucleotide phosphate (NADP)\/reduced NADP ratio and increased reduced glutathione\/oxidized glutathione ratio. Furthermore, SIRT3 enhanced oxidative phosphorylation (OxPhos) in AML cells under both basic and cytarabine\u2010treated conditions. A xenograft mouse model showed that SIRT3 overexpressing AML cells and patient\u2010derived xenograft mice bearing high SIRT3 deacetylase activity were more resistant to chemotherapy <jats:italic>in vivo<\/jats:italic>. SIRT3 inhibitor displayed synergy with cytarabine to ablate AML cells <jats:italic>in vitro<\/jats:italic> and in mouse models. Taken together, our study showed that SIRT3 is capable of reprograming mitochondrial metabolism towards OxPhos and downregulating ROS generation, which contribute to the chemoresistance of AML cells. SIRT3 can be utilized as a potential therapeutic target to improve the anti\u2010leukaemic efficacy of standard chemotherapeutic agents for AML.<\/jats:p>","DOI":"10.1111\/bjh.16044","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T18:13:18Z","timestamp":1561486398000},"page":"49-64","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["SIRT3 deacetylase activity confers chemoresistance in AML via regulation of mitochondrial oxidative phosphorylation"],"prefix":"10.1111","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8097-2202","authenticated-orcid":false,"given":"Jiao","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Cell Biology Shanghai Jiaotong University School of Medicine Shanghai 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