DNA Polymerase Gamma Recovers Mitochondrial Function and Inhibits Vascular Calcification by Interacted with p53.
DNA Polymerase Gamma Recovers Mitochondrial Function and Inhibits Vascular Calcification by Interacted with p53.
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DNA 聚合酶 Gamma 通过与 p53 相互作用恢复线粒体功能并抑制血管钙化
DOI：
10.7150/ijbs.65030
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发表时间：
2022
影响因子：
9.2
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Wang P;Wu B;You S;Lu S;Xiong S;Zou Y;Jia P;Guo X;Zhang Y;Cao L;Sun Y;Zhang N
DNA聚合酶γ（POLG）是线粒体DNA（mtDNA）的主要聚合酶，对于稳定线粒体功能至关重要。血管钙化（VC）是多种慢性疾病的终阶段的常见衰老相关退行性病理现象。在钙化血管中经常观察到线粒体功能障碍，但是POLG在钙化过程中的功能和机制仍然未知。本研究发现，POLGD257A/D257A小鼠的主动脉钙化比野生型（WT）小鼠具有维生素D3（VIT D3）治疗的严重钙化，并且在体外也证实了这种现象。从机械上讲，POLG可以在钙化条件下增强p53的募集和相互作用，以恢复线粒体功能并最终抵抗钙化。同时，我们发现突变体POLG（D257A）未能达到相同的救援效应，这表明3'-5'外核酸酶活性可以保证p53和POLG对钙化刺激的增强相互作用。因此，我们认为它是POLG，而不是突变的POLG可以保持线粒体功能并在体外和体内减轻钙化。 POLG可能是针对钙化的新型潜在治疗靶标，为临床治疗提供了新的见解。
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 PolGD257A/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.
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影响因子：
8
作者：
Bakthavatchalu, V.;Dey, S.;Xu, Y.;Noel, T.;Jungsuwadee, P.;Holley, A. K.;Dhar, S. K.;Batinic-Haberle, I.;St Clair, D. K.
通讯作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
20.3
作者：
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通讯作者：
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