Overexpression of PKM2 promotes mitochondrial fusion through attenuated p53 stability
Metrics: PDF 4069 views | HTML 1159 views | ?
Haili Wu1, Peng Yang1, Wanglai Hu3, Yingying Wang1, Yangxu Lu4, Lichao Zhang1, Yongsheng Fan2, Hong Xiao5, Zhuoyu Li1,2
1Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China
2College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
3Department of Immunology, School of Basic Medicine, Anhui Medical University, Hefei 230032, China
4College of Life Science, Shanxi University, Taiyuan 030006, China
5The first hospital of Shanxi Medical University, Taiyuan 030006, China
Haili Wu, email: email@example.com
Zhuoyu Li, email: firstname.lastname@example.org
Keywords: PKM2, Drp1, mitochondrial fusion, p53 stability
Received: January 28, 2016 Accepted: October 16, 2016 Published: October 27, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.