DNA Polymerase Gamma Recovers Mitochondrial Function and Inhibits Vascular Calcification by Interacted with P53

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2022 Jan 3

PMID 34975341

Authors

Pengbo Wang

Boquan Wu

Shilong You

Saien Lu

Shengjun Xiong

Yuanming Zou

Pengyu Jia

Xiaofan Guo

Ying Zhang

Liu Cao

Yingxian Sun

Naijin Zhang

Affiliations

Soon will be listed here.

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 mice presented more severe calcification of aortas than wild type (WT) mice with vitamin D3 (Vit D3) treatment, and this phenomenon was also confirmed . 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 and . And PolG could be a novel potential therapeutic target against calcification, providing a novel insight to clinical treatment.

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