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

Shubhranshu S. Gupta, Robert Sharp, Colby Hofferek, Le Kuai, Gerald W. Dorn, Jin Wang, Min Chen

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1862-1877.e7
JournalCell Reports
Volume29
Issue number7
DOIs
StatePublished - Nov 12 2019

Keywords

  • autophagy
  • CD8 T cells
  • effector memory cells
  • fatty acid metabolism
  • HIF1α
  • long-chain fatty acid oxidation
  • mitochondrial superoxide
  • mitophagy
  • NIX
  • short/branched-chain fatty acid oxidation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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