Screening of CPT1A-Targeting Lipid Metabolism Modulators Using Mitochondrial Membrane Chromatography

Wu Su, Fanding Xu, Jinjin Zhong, Ranrui Hu, Lizhuo Wang, Hua Li, Zhiwei Yang, Shuai Ge, Huaizhen He, Shengli Han, Xiuying Xie, Hui Guo, Langchong He, Jiankang Liu, Tao Yi, Yu Kong, Jiangang Long

Research output: Contribution to journalArticlepeer-review


Carnitine palmitoyltransferase 1A (CPT1A), which resides on the mitochondrial outer membrane, serves as the rate-limiting enzyme of fatty acid β-oxidation. Identifying the compounds targeting CPT1A warrants a promising candidate for modulating lipid metabolism. In this study, we developed a CPT1A-overexpressed mitochondrial membrane chromatography (MMC) to screen the compounds with affinity for CPT1A. Cells overexpressing CPT1A were cultured, and subsequently, their mitochondrial membrane was isolated and immobilized on amino-silica gel cross-linked by glutaraldehyde. After packing the mitochondrial membrane column, retention components of MMC were performed with LC/MS, whose analytic peaks provided structural information on compounds that might interact with mitochondrial membrane proteins. With the newly developed MMC-LC/MS approach, several Chinese traditional medicine extracts, such as Scutellariae Radix and Polygoni Cuspidati Rhizoma et Radix (PCRR), were analyzed. Five noteworthy compounds, baicalin, baicalein, wogonoside, wogonin, and resveratrol, were identified as enhancers of CPT1A enzyme activity, with resveratrol being a new agonist for CPT1A. The study suggests that MMC serves as a reliable screening system for efficiently identifying modulators targeting CPT1A from complex extracts.

Original languageEnglish
Pages (from-to)13234-13246
Number of pages13
JournalACS applied materials & interfaces
Issue number10
Publication statusPublished - 13 Mar 2024


  • CPT1A
  • Chinese traditional medicine
  • lipid metabolism
  • mitochondrial membrane chromatography
  • mitochondrion-target molecule screening


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