title: Overexpression of PKM2 promotes mitochondrial fusion through attenuated p53 stability.
abstract: M2-type pyruvate kinase (PKM2) contributes to the Warburg effect. However, it remains unknown as to whether PKM2 has an inhibitory effect on mitochondrial function. We report in this work that PKM2 overexpression inhibits the expression of Drp1 and results in the mitochondrial fusion. The ATP production was found to be decreased, the mtDNA copy number elevated and the expression level of electron transport chain (ETC) complex I, III, V depressed in PKM2 overexpressed cells. PKM2 overexpression showed a decreased p53 protein level and a shorter p53 half-life. In contrast, PKM2 knockdown resulted in increased p53 expression and prolonged half-life of p53. PKM2 could directly bind with both p53 and MDM2 and promote MDM2-mediated p53 ubiquitination. The dimeric PKM2 significantly suppressed p53 expression compared with the other PKM2 mutants. The reverse relationship between PKM2 and Drp1 was further confirmed in a large number of clinical samples. Taken together, the present results highlight a new mechanism that link PKM2 to mitochondrial function, based on p53-Drp1 axis down regulation, revealing a novel therapeutic target in patients with abnormal mitochondria.
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Haili
authors: H
authors: Wu
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Peng
authors: P
authors: Yang
authors: Department of Immunology, School of Basic Medicine, Anhui Medical University, Hefei 230032, China.
authors: Wanglai
authors: W
authors: Hu
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Yingying
authors: Y
authors: Wang
authors: College of Life Science, Shanxi University, Taiyuan 030006, China.
authors: Yangxu
authors: Y
authors: Lu
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Lichao
authors: L
authors: Zhang
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors: Yongsheng
authors: Y
authors: Fan
authors: The First Hospital of Shanxi Medical University, Taiyuan 030006, China.
authors: Hong
authors: H
authors: Xiao
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.|College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors: Zhuoyu
authors: Z
authors: Li
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000502:physiology*; D013963:Thyroid Hormones / Q000096:biosynthesis* / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D013963:Thyroid Hormones; D016159:Tumor Suppressor Protein p53; D000097810:Thyroid Hormone-Binding Proteins; C495901:TP53 protein, human
keywords: Drp1; PKM2; mitochondrial fusion; p53 stability