Recognition of cytosolic DNA attenuates glucose metabolism and induces AMPK mediated energy stress response

Int J Biol Sci. 2015 Apr 5;11(5):587-94. doi: 10.7150/ijbs.10945. eCollection 2015.

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.

Keywords: AMPK; ATP depletion; Cytosolic DNA; Energy stress; Glycolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Cytosol / metabolism*
  • DNA / metabolism*
  • Energy Metabolism / physiology*
  • Gene Expression Regulation / physiology
  • Glucose / metabolism*
  • HEK293 Cells
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / metabolism
  • Poly A
  • Stress, Physiological / physiology*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Membrane Proteins
  • Multiprotein Complexes
  • STING1 protein, human
  • Poly A
  • poly(dA)
  • DNA
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • AMP-Activated Protein Kinases
  • Nucleotidyltransferases
  • cGAS protein, human
  • Glucose