Succinate-driven PKM2 succinylation and dimerization accelerates age-associated cardiac fibrosis.

Ziwen Wang, Ziyuan Zhang, Zheng Ping, Shu Yang, Yaqi Li, Ting Jiang, Xin Zheng, Qi Zhang, Zhaochuan Liu, Xiaoli Zhang, Zhongyong Jiang, Deng Li, Haimei Sun, Bo Wu, Deshan Zhou, Xuebin Cao, Hanping Shi, Tingyi Sun

Department of Cardiology and Nephrology, The 82nd Group Army Hospital of PLA (252 Hospital of PLA), Baoding, Hebei Province, China. [email protected] of Cardiology and Nephrology, The 82nd Group Army Hospital of PLA (252 Hospital of PLA), Baoding, Hebei Province, China. [email protected]. · pubmed

Paper

Abstract

Age-related cardiac fibrosis is a key driver of heart failure and hallmark of aging whose mechanisms remain incompletely understood. Here we show elevated succinate levels in aged mice and humans drive cardiac fibrosis by enhancing fibroblast activation and collagen production. This process is mediated through succinate-dependent succinylation of PKM2 at lysine 125, promoting its transition from tetrameric to dimeric states. Using SUCNR1

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Research summary

Elevated succinate levels drive cardiac fibrosis through succinylation of PKM2, promoting its dimerization. This research addresses a mechanism underlying age-related cardiac fibrosis, which is a significant aspect of aging and heart failure, thus contributing to the understanding of age-related diseases.

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