Pcx, the gene encoding pyruvate carboxylase, is a catalytic enzyme within mitochondria. Pyruvate carboxylase is intricately linked with mitochondrial damage and metabolism, playing a role in various metabolic pathways [1].

In a study on renal fibrosis, renal proximal tubule-specific Pcx gene knockout mice (PcxcKO) showed significant interstitial fibrosis compared to control mice, with heightened expression of extracellular matrix molecules. Mechanistically, PC deficiency reduces its interaction with sulfide:quinone oxidoreductase (SQOR), leading to mitochondrial morphological and functional disruption, increased mtDNA release, activation of the cGAS-STING pathway, elevated glycolysis levels, and ultimately promoting renal fibrosis [1].

In conclusion, Pcx plays a crucial role in maintaining mitochondrial function and metabolism. The PcxcKO mouse model has revealed its significance in renal fibrosis, providing a novel theoretical foundation and potential therapeutic targets for understanding the pathogenesis and treatment of this disease.

References:

1. Huang, Hao, Han, Yuanyuan, Zhang, Yan, Tao, Lijian, Peng, Zhangzhe. 2025. Deletion of Pyruvate Carboxylase in Tubular Epithelial Cell Promotes Renal Fibrosis by Regulating SQOR/cGAS/STING-Mediated Glycolysis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2408753. doi:10.1002/advs.202408753. https://pubmed.ncbi.nlm.nih.gov/39836535/