Full Text | PDF

Int J Biol Sci 2022; 18(1):409-425. doi:10.7150/ijbs.65030 This issue Cite

Research Paper

DNA Polymerase Gamma Recovers Mitochondrial Function and Inhibits Vascular Calcification by Interacted with p53

Pengbo Wang¹, Boquan Wu¹, Shilong You¹, Saien Lu¹, Shengjun Xiong¹, Yuanming Zou¹, Pengyu Jia¹, Xiaofan Guo¹, Ying Zhang^1✉, Liu Cao^2✉, Yingxian Sun^1✉, Naijin Zhang^1✉

1. Department of Cardiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, People Republic of China.
2. College of Basic Medical Science, Institute of Translational Medicine, Key Laboratory of Medical Cell Biology, Ministry of Education, Key Laboratory of Liaoning Province, China Medical University, Shenyang, 110122, Liaoning Province, People Republic of China.

✉ Corresponding authors: Naijin Zhang, Department of Cardiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, People Republic of China. Tel: +86 15040171605, E-mail: njzhangedu.cn. Yingxian Sun, Department of Cardiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, People Republic of China. Tel: +86 13804068889, E-mail: yxsunedu.cn. Liu Cao, College of Basic Medical Science, Institute of Translational Medicine, Key Laboratory of Medical Cell Biology, Ministry of Education, Key Laboratory of Liaoning Province, China Medical University, Shenyang, 110122, Liaoning Province, People Republic of China. Tel: +86 (024) 31939630, E-mail: lcaoedu.cn. Ying Zhang, Department of Cardiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, People Republic of China. Tel: +86 +86 13224130039, E-mail: yzhang02edu.cn. More

Abstract

DNA polymerase gamma (PolG) is the major polymerase of mitochondrial DNA (mtDNA) and essential for stabilizing mitochondrial function. Vascular calcification (VC) is common senescence related degenerative pathology phenomenon in the end-stage of multiple chronic diseases. Mitochondrial dysfunction was often observed in calcified vessels, but the function and mechanism of PolG in the calcification process was still unknown. The present study found PolG^D257A/D257A mice presented more severe calcification of aortas than wild type (WT) mice with vitamin D3 (Vit D3) treatment, and this phenomenon was also confirmed in vitro. Mechanistically, PolG could enhance the recruitment and interaction of p53 in calcification condition to recover mitochondrial function and eventually to resist calcification. Meanwhile, we found the mutant PolG (D257A) failed to achieve the same rescue effects, suggesting the 3'-5' exonuclease activity guarantee the enhanced interaction of p53 and PolG in response to calcification stimulation. Thus, we believed that it was PolG, not mutant PolG, could maintain mitochondrial function and attenuate calcification in vitro and in vivo. And PolG could be a novel potential therapeutic target against calcification, providing a novel insight to clinical treatment.

Keywords: DNA polymerase gamma, mitochondria, calcification, p53

Citation styles

©2024 Ivyspring International Publisher. Terms of use