title: Recognition of cytosolic DNA attenuates glucose metabolism and induces AMPK mediated energy stress response.
abstract: Both viral infection and DNA transfection expose single-stranded or double-stranded DNA to the cytoplasm of mammalian cells. Recognition of cytosolic DNA activates a series of cellular responses, including induction of pro-inflammatory genes such as type I interferon through the well-known cGAS-STING pathway. Here we show for the first time that intracellular administration of either single or double stranded interferon stimulating DNA (ISD), but not poly(dA) suppresses cell growth in many different cell types. Suppression of cell growth by cytosolic DNA is cGAS/STING independent and associated with inhibition of glucose metabolism, ATP depletion and subsequent cellular energy stress responses including activation of AMPK and inactivation of mTORC1. Our results suggest that in concert with but independent of innate immune response, recognition of cytosolic DNA induced cellular energy stress potentially functions as a metabolic barrier to viral replication.
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China. ; 2. Translational Medicine Institute, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China. ; 3. Department of Bioengineering, Fujian Vocational College of Bioengineering, Fuzhou, Fujian, 350007, China.
authors.forename: Linna
authors.initials: L
authors.lastname: Xie
authors.affiliation: 4. State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
authors.forename: Yaoji
authors.initials: Y
authors.lastname: Liang
authors.affiliation: 4. State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
authors.forename: Suqin
authors.initials: S
authors.lastname: Wu
authors.affiliation: 2. Translational Medicine Institute, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Xu
authors.affiliation: 2. Translational Medicine Institute, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Yuedong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 2. Translational Medicine Institute, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Hekun
authors.initials: H
authors.lastname: Liu
authors.affiliation: 1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350108, China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Lin
authors.affiliation: 4. State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
authors.affiliation: 2. Translational Medicine Institute, Fujian Medical University, Fuzhou, Fujian, 350108, China. ; 5. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kunping
authors.initials: K
authors.lastname: Lu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D011061:Poly A; D013312:Stress, Physiological / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D055372:AMP-Activated Protein Kinases; D004247:DNA; D005947:Glucose; D000076222:Mechanistic Target of Rapamycin Complex 1; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009713:Nucleotidyltransferases; D011061:Poly A; D058570:TOR Serine-Threonine Kinases; C532857:STING1 protein, human; D000099197:STING Protein; C015465:poly(dA); C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
keywords: AMPK; ATP depletion; Cytosolic DNA; Energy stress; Glycolysis