Professor Li Peng, president of Zhengzhou University (ZZU), has co-authored a landmark study published in the journal Nature under the title "CLCC1 Governs ER Bilayer Equilibration to Maintain Lipid Homeostasis". The research identifies CLCC1 as a key sensor governing lipid bilayer equilibrium in the endoplasmic reticulum (ER), solving a long-standing puzzle in cell biology regarding how lipid orientation is controlled.
Lipid metabolism is critical for cellular and organismal health, and its dysregulation underlies major diseases such as cardiovascular and neurodegenerative disorders. Using advanced techniques like cryo-electron tomography (cryo-ET) and integrative proteomics, the team discovered that CLCC1 senses lipid bilayer imbalance in the ER and interacts with TMEM41B to coordinate the distribution of phospholipids and neutral lipids. Loss of CLCC1 leads to severe bilayer disruption and formation of aberrant giant lipid droplets. Genetic analyses revealed that human CLCC1 variants correlate with blood lipid levels, and in mouse models, liver-specific CLCC1 inactivation nearly eliminated fasting-induced lipid mobilization.
Interestingly, CLCC1 can polymerize and relocate to imbalanced lipid regions, suggesting a working model in which it acts as both sensor and recruiter of effectors to maintain ER homeostasis.
A coinciding Nature paper from University of California, Berkeley confirmed CLCC1's central role in lipid flux and nuclear pore assembly, underscoring the fundamental importance of ER bilayer regulation.
This collaborative work, involving teams from Peking University, provides new insights into lipid metabolism disorders and opens potential avenues for therapeutic intervention in related diseases.
The ZZU team publishes a breakthrough study in Nature on lipid homeostasis regulation. [Photo/zzu.edu.cn]