Zhou Min, Qin Ziqi, Zhu Xiting, Ruan Yifeng, Ling Huiling, Li Chen, Gan Xueqi
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
J Physiol Biochem. 2025 Feb;81(1):21-34. doi: 10.1007/s13105-025-01068-9. Epub 2025 Mar 21.
Pyruvate dehydrogenase kinases (PDKs) can regulate the conversion of pyruvate to acetyl coenzyme A through the mitochondrial pyruvate dehydrogenase complex (PDHC). As the rate-limiting enzymes of PDHC, PDKs link glycolysis to the tricarboxylic acid cycle. Pathological changes in many diseases involve alterations in cellular metabolism, which are partly reflected in changes in mitochondrial function. The intermediate role of PDKs in metabolic processes allows for the influence of both glycolysis and oxidative phosphorylation. Recent studies have shown that PDKs play a crucial role in regulating metabolic reprogramming, mitochondrial function and cellular activities in both oncological studies and various non-oncological diseases. This paper aims to clarify the molecular regulatory mechanisms of PDKs; review the relationship of PDKs with cellular metabolic reprogramming, regulation of ROS, and apoptosis; and the present status of research on PDKs in osteoporosis, diabetes mellitus, and vascular diseases. With this review, we have increased our understanding and insight at the molecular level, providing new insights into targeting PDKs to reverse metabolism-related diseases.
丙酮酸脱氢酶激酶（PDKs）可通过线粒体丙酮酸脱氢酶复合物（PDHC）调节丙酮酸向乙酰辅酶A的转化。作为PDHC的限速酶，PDKs将糖酵解与三羧酸循环联系起来。许多疾病的病理变化涉及细胞代谢的改变，这部分反映在线粒体功能的变化上。PDKs在代谢过程中的中间作用使得其对糖酵解和氧化磷酸化均有影响。最近的研究表明，在肿瘤学研究和各种非肿瘤性疾病中，PDKs在调节代谢重编程、线粒体功能和细胞活动方面发挥着关键作用。本文旨在阐明PDKs的分子调控机制；综述PDKs与细胞代谢重编程、活性氧调节及细胞凋亡的关系；以及PDKs在骨质疏松症、糖尿病和血管疾病中的研究现状。通过这篇综述，我们在分子水平上增进了理解和认识，为靶向PDKs逆转代谢相关疾病提供了新的见解。
