NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8 + T Cells

Cell Rep. 2019 Nov 12;29(7):1862-1877.e7. doi: 10.1016/j.celrep.2019.10.032.

Abstract

Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8+ T cells remain unclear. Here we show that deficiency in NIX-dependent mitophagy leads to metabolic defects in effector memory T cells. Deletion of NIX caused HIF1α accumulation and altered cellular metabolism from long-chain fatty acid to short/branched-chain fatty acid oxidation, thereby compromising ATP synthesis during effector memory formation. Preventing HIF1α accumulation restored long-chain fatty acid metabolism and effector memory formation in antigen-specific CD8+ T cells. Our study suggests that NIX-mediated mitophagy is critical for effector memory formation in T cells.

Keywords: CD8(+) T cells; HIF1α; NIX; autophagy; effector memory cells; fatty acid metabolism; long-chain fatty acid oxidation; mitochondrial superoxide; mitophagy; short/branched-chain fatty acid oxidation.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Immunologic Memory*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / immunology*
  • Mitophagy / genetics
  • Mitophagy / immunology*

Substances

  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Proteins
  • Mitochondrial Proteins
  • Nix protein, mouse