Reliance on Cox10 and oxidative metabolism for antigen-specific NK cell expansion

Cell Rep. 2021 Jun 1;35(9):109209. doi: 10.1016/j.celrep.2021.109209.


Natural killer (NK) cell effector functions are dependent on metabolic regulation of cellular function; however, less is known about in vivo metabolic pathways required for NK cell antiviral function. Mice with an inducible NK-specific deletion of Cox10, which encodes a component of electron transport chain complex IV, were generated to investigate the role of oxidative phosphorylation in NK cells during murine cytomegalovirus (MCMV) infection. Ncr1-Cox10Δ/Δ mice had normal numbers of NK cells but impaired expansion of antigen-specific Ly49H+ NK cells and impaired NK cell memory formation. Proliferation in vitro and homeostatic expansion were intact, indicating a specific metabolic requirement for antigen-driven proliferation. Cox10-deficient NK cells upregulated glycolysis, associated with increased AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) activation, although this was insufficient to protect the host. These data demonstrate that oxidative metabolism is required for NK cell antiviral responses in vivo.

Keywords: Cox10; NK cells; metabolism; murine cytomegalovirus; oxidative phosphorylation; proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism
  • Alkyl and Aryl Transferases / deficiency
  • Alkyl and Aryl Transferases / metabolism*
  • Animals
  • Antigens / metabolism*
  • Cell Proliferation
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology
  • Enzyme Activation
  • Gene Deletion
  • Immunologic Memory
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / enzymology
  • Killer Cells, Natural / metabolism*
  • Ligands
  • Membrane Proteins / deficiency
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Muromegalovirus / physiology
  • Oxidation-Reduction
  • Phenotype
  • RNA-Seq
  • Single-Cell Analysis
  • TOR Serine-Threonine Kinases / metabolism


  • Antigens
  • Ligands
  • Membrane Proteins
  • Alkyl and Aryl Transferases
  • COX10 protein, mouse
  • TOR Serine-Threonine Kinases
  • Adenylate Kinase