2. Academic Validation
  3. Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes

Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes

  • EMBO J. 2024 Dec;43(24):6383-6409. doi: 10.1038/s44318-024-00288-x.
Min Xu # 1,  Zi-Yue Chen # 2,  Yang Li # 3 4,  Yue Li 1,  Ge Guo 1,  Rong-Zheng Dai 1,  Na Ni 1,  Jing Tao 3 4,  Hong-Yu Wang 2,  Qiao-Li Chen 2,  Hua Wang 5,  Hong Zhou 6,  Yi-Ning Yang 7 8 9 10,  Shuai Chen 11,  Liang Chen 12 13
Affiliations

Affiliations

  • 1 College of Life Sciences, Anhui Medical University, 230032, Hefei, China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, 210061, Nanjing, China.
  • 3 Department of Cardiology, People's Hospital of Xinjiang Uyghur Autonomous Region, 830000, Urumqi, China.
  • 4 Xinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research, 830000, Urumqi, China.
  • 5 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 230022, Hefei, China.
  • 6 College of Life Sciences, Anhui Medical University, 230032, Hefei, China. hzhou@ahmu.edu.cn.
  • 7 Department of Cardiology, People's Hospital of Xinjiang Uyghur Autonomous Region, 830000, Urumqi, China. yangyn5126@xjrmyy.com.
  • 8 Xinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research, 830000, Urumqi, China. yangyn5126@xjrmyy.com.
  • 9 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, 830000, Urumqi, China. yangyn5126@xjrmyy.com.
  • 10 Key Laboratory of Cardiovascular Disease Research, First Affiliated Hospital of Xinjiang Medical University, 830000, Urumqi, China. yangyn5126@xjrmyy.com.
  • 11 State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, 210061, Nanjing, China. chenshuai@nju.edu.cn.
  • 12 College of Life Sciences, Anhui Medical University, 230032, Hefei, China. liang-chen@ahmu.edu.cn.
  • 13 Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, 230001, Hefei, China. liang-chen@ahmu.edu.cn.
  • # Contributed equally.
PMID: 39496977 DOI: 10.1038/s44318-024-00288-x
Abstract

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.

Keywords

17-Beta-hydroxysteroid Dehydrogenase 13; AMP-activated Protein Kinase; Organelle Interactions; Ras-related Protein Rab-2A; Very-low-density Lipoprotein.

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