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Recognition of Cytosolic DNA Attenuates Glucose Metabolism and Induces AMPK Mediated Energy Stress Response
- Source :
- International Journal of Biological Sciences
- Publication Year :
- 2015
- Publisher :
- Ivyspring International Publisher, 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.
- Subjects :
- ATP depletion
AMPK
mTORC1
AMP-Activated Protein Kinases
Mechanistic Target of Rapamycin Complex 1
Cytosolic DNA
Applied Microbiology and Biotechnology
chemistry.chemical_compound
Cytosol
AMP-activated protein kinase
Stress, Physiological
Interferon
medicine
Humans
Molecular Biology
Ecology, Evolution, Behavior and Systematics
biology
Cell growth
TOR Serine-Threonine Kinases
Energy stress
HEK 293 cells
Membrane Proteins
DNA
Cell Biology
Nucleotidyltransferases
Molecular biology
Cell biology
Glucose
HEK293 Cells
Gene Expression Regulation
chemistry
Multiprotein Complexes
biology.protein
Energy Metabolism
Poly A
Glycolysis
Intracellular
Research Paper
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 14492288
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Sciences
- Accession number :
- edsair.doi.dedup.....982f35b9a9508c18f36b0bc08aa9a284