Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes
Lipid droplets (LDs) serve as crucial hubs for lipid trafficking and metabolic regulation through their numerous interactions with various organelles. While the interplay between LDs and the Golgi apparatus has been recognized, their roles and underlying mechanisms remain poorly understood. Here, we reveal the role of Ras-related protein Rab-2A (Rab2A) in mediating LD-Golgi interactions, thereby contributing to very-low-density lipoprotein (VLDL) lipidation and secretion in hepatocytes. Mechanistically, our findings identify a selective interaction between Golgi-localized Rab2A and 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) protein residing on LDs. This complex facilitates dynamic organelle communication between the Golgi apparatus and LDs, thus contributing to lipid transfer from LDs to the Golgi apparatus for VLDL2 lipidation and secretion. Attenuation of Rab2A activity via AMP-activated protein kinase (AMPK) suppresses the Rab2A-HSD17B13 complex formation, impairing LD-Golgi interactions and subsequent VLDL secretion. Furthermore, genetic inhibition of Rab2A and HSD17B13 in the liver reduces the serum triglyceride and cholesterol levels. Collectively, this study provides a new perspective on the interactions between the Golgi apparatus and LDs.
Authors
- Ziyue Chen (ORCID: https://orcid.org/0009-0003-5348-0239)
- Rongping Dai (ORCID: https://orcid.org/0000-0002-7901-5998)
- Yi‐Ning Yang (ORCID: https://orcid.org/0000-0002-8332-8508)
- Yue Li (ORCID: https://orcid.org/0000-0003-3747-1482)
- Shuai Chen (ORCID: https://orcid.org/0000-0002-8511-911X)
- Hua Wang (ORCID: https://orcid.org/0000-0002-2605-5697)
- Yang Li (ORCID: https://orcid.org/0000-0001-7242-4687)
- Hongyu Wang (ORCID: https://orcid.org/0000-0001-7334-9439)
- Hong Zhou (ORCID: https://orcid.org/0000-0001-5350-4681)
- Tao Jing (ORCID: https://orcid.org/0000-0003-1936-4392)
- Min Xu (ORCID: https://orcid.org/0000-0003-3930-8718)
- Qiaoli Chen (ORCID: https://orcid.org/0000-0002-0102-1351)
- Na Ni (ORCID: https://orcid.org/0000-0003-1914-0604)
- Guo Ge (ORCID: https://orcid.org/0000-0002-6362-772X)
- Liang Chen (ORCID: https://orcid.org/0000-0002-8331-8350)
Institutions
- Xinjiang Medical University (CN)
- Anhui Medical University (CN)
- First Affiliated Hospital of Xinjiang Medical University (CN)
- Xinjiang Uygur Autonomous Region Product Quality Supervision and Inspection Institute (CN)
- People's Hospital of Xinjiang Uygur Autonomous Region (CN)
- Model Animal Research Center (CN)
- First Affiliated Hospital of Anhui Medical University (CN)
- Xinjiang University (CN)
Publication Details
- Journal
- The EMBO Journal
- Published
- 2024-11-04
- DOI
- https://doi.org/10.1038/s44318-024-00288-x
- Citations
- 10
- Primary Topic
- Lipid metabolism and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 2.95
Funders
- National Natural Science Foundation of China
- Anhui Medical University
- Anhui Provincial Department of Education
- Natural Science Foundation of Anhui Province