title: STAT3 Undergoes Acetylation-dependent Mitochondrial Translocation to Regulate Pyruvate Metabolism.
abstract: Cytoplasmic STAT3, after activation by growth factors, translocates to different subcellular compartments, including nuclei and mitochondria, where it carries out different biological functions. However, the precise mechanism by which STAT3 undergoes mitochondrial translocation and subsequently regulates the tricarboxylic acid (TCA) cycle-electron transport chain (ETC) remains poorly understood. Here, we clarify this process by visualizing STAT3 acetylation in starved cells after serum reintroduction or insulin stimulation. CBP-acetylated STAT3 undergoes mitochondrial translocation in response to serum introduction or insulin stimulation. In mitochondria, STAT3 associates with the pyruvate dehydrogenase complex E1 (PDC-E1) and subsequently accelerates the conversion of pyruvate to acetyl-CoA, elevates the mitochondrial membrane potential, and promotes ATP synthesis. SIRT5 deacetylates STAT3, thereby inhibiting its function in mitochondrial pyruvate metabolism. In the A549 lung cancer cell line, constitutively acetylated STAT3 localizes to mitochondria, where it maintains the mitochondrial membrane potential and ATP synthesis in an active state.
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan, 250012, China.
authors.forename: Yan S
authors.initials: YS
authors.lastname: Xu
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan, 250012, China.
authors.forename: Jinyuan J
authors.initials: JJ
authors.lastname: Liang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan, 250012, China.|The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Xiang-Zhong J
authors.initials: XJ
authors.lastname: Zhao
authors.affiliation: Department of Immune Diseases, School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan, 250012, China.
authors.forename: Ye-Yang
authors.initials: YY
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Quanli C
authors.initials: QC
authors.lastname: Zou
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Junxun M
authors.initials: JM
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Cheng-E
authors.initials: CE
authors.lastname: Tu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Yan-Ge
authors.initials: YG
authors.lastname: Cui
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.|Translational Medicine Center, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Cancer Research Center, Shandong University School of Medicine, Jinan, 250012, China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institutes of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chin
mesh_terms: D000072283:A549 Cells; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002952:Citric Acid Cycle; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid