2. Academic Validation
  3. CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress

CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress

  • Cell Metab. 2019 Jul 2;30(1):157-173.e7. doi: 10.1016/j.cmet.2019.05.009.
Qidong Li 1,  Yichun Wang 1,  Shuang Wu 2,  Zhong Zhou 1,  Xiaojuan Ding 2,  Ronghua Shi 1,  Rick F Thorne 3,  Xu Dong Zhang 4,  Wanglai Hu 5,  Mian Wu 6
Affiliations

Affiliations

  • 1 The Chinese Academy of Sciences (CAS), Key Laboratory of Innate Immunity & Chronic Disease, CAS Center for Excellence in Cell & Molecular Biology, School of Life Sciences, University of Science & Technology of China, Hefei 230026, China.
  • 2 Department of Immunology, Anhui Medical University, Hefei 230027, China.
  • 3 Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou 450003, China; Key Laboratory of Stem Cell Differentiation & Modification, School of Clinical Medicine, Henan University, Zhengzhou 450003, China; School of Environmental & Life Sciences, University of Newcastle, Newcastle, NSW 2258, Australia.
  • 4 Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou 450003, China; Key Laboratory of Stem Cell Differentiation & Modification, School of Clinical Medicine, Henan University, Zhengzhou 450003, China; School of Biomedical Sciences & Pharmacy, University of Newcastle, Newcastle, NSW 2308, Australia.
  • 5 Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou 450003, China; Key Laboratory of Stem Cell Differentiation & Modification, School of Clinical Medicine, Henan University, Zhengzhou 450003, China; Department of Immunology, Anhui Medical University, Hefei 230027, China. Electronic address: wanglaihu@ahmu.edu.cn.
  • 6 The Chinese Academy of Sciences (CAS), Key Laboratory of Innate Immunity & Chronic Disease, CAS Center for Excellence in Cell & Molecular Biology, School of Life Sciences, University of Science & Technology of China, Hefei 230026, China; Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou 450003, China; Key Laboratory of Stem Cell Differentiation & Modification, School of Clinical Medicine, Henan University, Zhengzhou 450003, China. Electronic address: wumian@ustc.edu.cn.
PMID: 31155494 DOI: 10.1016/j.cmet.2019.05.009
Abstract

We report that circACC1, a circular RNA derived from human ACC1, plays a critical role in cellular responses to metabolic stress. CircACC1 is preferentially produced over ACC1 in response to serum deprivation by the transcription factor c-Jun. It functions to stabilize and promote the enzymatic activity of the AMPK holoenzyme by forming a ternary complex with the regulatory β and γ subunits. The cellular levels of circACC1 modulate both fatty acid β-oxidation and glycolysis, resulting in profound changes in cellular lipid storage. In a tumor xenograft model, silencing or enforced expression of circACC1 resulted in growth inhibition and enhancement, respectively. Moreover, increased AMPK activation in colorectal Cancer tissues was frequently associated with elevated circACC1 expression. We conclude that circACC1 serves as an economic means to elicit AMPK activation and moreover propose that Cancer cells exploit circACC1 during metabolic reprogramming.

Keywords

AMPK; c-Jun; circACC1; circular RNA; fatty acid β oxidation; glycolysis; lipid metabolism; metabolic reprogramming; non-coding RNA; serum deprivation.

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