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


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 HIF1? 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 HIF1? 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.

SUBMITTER: Gupta SS 

PROVIDER: S-EPMC6886713 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8<sup>+</sup> T Cells.

Gupta Shubhranshu S SS   Sharp Robert R   Hofferek Colby C   Kuai Le L   Dorn Gerald W GW   Wang Jin J   Chen Min M  

Cell reports 20191101 7


Autophagy plays a critical role in the maintenance of immunological memory. However, the molecular mechanisms involved in autophagy-regulated effector memory formation in CD8<sup>+</sup> 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 synthe  ...[more]

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