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

doi:10.1016/j.celrep.2019.10.032

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

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30 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 language	English
Pages (from-to)	1862-1877.e7
Journal	Cell Reports
Volume	29
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2019.10.032
State	Published - Nov 12 2019

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

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10.1016/j.celrep.2019.10.032

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title = "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 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",

author = "Gupta, {Shubhranshu S.} and Robert Sharp and Colby Hofferek and Le Kuai and Dorn, {Gerald W.} and Jin Wang and Min Chen",

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doi = "10.1016/j.celrep.2019.10.032",

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AU - Gupta, Shubhranshu S.

AU - Sharp, Robert

AU - Hofferek, Colby

AU - Kuai, Le

AU - Dorn, Gerald W.

AU - Wang, Jin

AU - Chen, Min

PY - 2019/11/12

Y1 - 2019/11/12

N2 - 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.

AB - 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.

KW - CD8 T cells

KW - HIF1α

KW - NIX

KW - autophagy

KW - effector memory cells

KW - fatty acid metabolism

KW - long-chain fatty acid oxidation

KW - mitochondrial superoxide

KW - mitophagy

KW - short/branched-chain fatty acid oxidation

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JO - Cell Reports

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ER -

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

Abstract

Keywords

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