Gunes Parlakgul

Gunes Parlakgul, MD, Assistant Professor, Department of Metabolic Biology and Nutrition, University of California, Berkeley

Research Description: My laboratory investigates how the spatial organization of organelles regulates cellular metabolism and contributes to metabolic disease. Our work has established that organelles, particularly the endoplasmic reticulum (ER) and mitochondria, dynamically remodel their architecture and interactions in response to metabolic demands, and that disruption of this organization contributes to insulin resistance, dysregulated hepatic glucose and lipid metabolism, and obesity-associated metabolic disease. We combine high-resolution volumetric imaging, AI-based image analysis, functional genomics, biochemistry and in vivo physiology to uncover the molecular mechanisms linking subcellular architecture to metabolic function. A major focus of our current research is defining how ER organization and its molecular machinery control hepatic glucose production and insulin sensitivity, with the goal of identifying previously unrecognized mechanisms and therapeutic targets for type 2 diabetes.

Selected relevant publications (SDRC members in BOLD):

  1. Artico LL*, Hakam S*, Parlakgül G#, Arruda AP#. Endoplasmic reticulum architecture in liver metabolic regulation.
    Trends in Cell Biology. 2026 Apr 7:S0962-8924(26)00035-8.

  2. Parlakgül G*, Arruda AP*, Pang S, Cagampan E, Min N, Güney E, Lee GY, Inouye K, Hess HF, Xu CS, Hotamışlıgil GS. Regulation of liver subcellular architecture controls metabolic homeostasis.
    Nature. 2022 Mar;603(7902):736-742.

  3. Parlakgül G, Pang S, Artico LL, Min N, Cagampan E, Villa R, Goncalves RLS, Lee GY, Xu CS, Hotamışlıgil GS*, Arruda AP*. Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity.
    Nature Communications. 2024 May 10;15(1):3982.

  4. Mathiowetz AJ*, Meymand ES*, Parlakgül G, van Hilten N, Torres EF, Artico LL, Deol KK, Lange M, Pang SP, Doubravsky CE, Roberts MA, Jorgens DM, Zalpuri R, Kang M, Boone C, Parks BW, Zhang Y, Morgens DW, Newman ET, Zhou Y, Talukdar S, Grabe M, Ku G, Levine TP, Arruda AP#, Olzmann JA#. CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly.
    Nature. 2026 Apr;652(8109):462-470.

  5. Goncalves RLS, Wang ZB, Riveros JK, Parlakgül G, Inouye KE, Lee GY, Fu X, Saksi J, Rosique C, Hui ST, Coll M, Arruda AP, Burgess SC, Graupera I, Hotamışlıgil GS. CoQ imbalance drives reverse electron transport to disrupt liver metabolism.
    Nature. 2025 Jul;643(8073):1057-1065.

  6. Shrestha N, Torres M, Zhang J, Lu Y, Haataja L, Reinert RB, Knupp J, Chen YJ, Parlakgul G, Arruda AP, Tsai B, Arvan P, Qi L. Integration of ER protein quality control mechanisms defines β cell function and ER architecture.
    J Clin Invest. 2023 Jan 3;133(1):e163584.