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

Research output: Contribution to journal › Article › peer-review

39 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 (US)
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

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

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2019.10.032

Cite this

@article{408c5534a41640a0b4a368622544638e,

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 = "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",

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

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = nov,

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

language = "English (US)",

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T1 - NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8+ T Cells

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 - autophagy

KW - CD8 T cells

KW - effector memory cells

KW - fatty acid metabolism

KW - HIF1α

KW - long-chain fatty acid oxidation

KW - mitochondrial superoxide

KW - mitophagy

KW - NIX

KW - short/branched-chain fatty acid oxidation

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