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

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 mem...

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Autores principales: Gupta, Shubhranshu S., Sharp, Robert, Hofferek, Colby, Kuai, Le, Dorn, Gerald W., Wang, Jin, Chen, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886713/
https://www.ncbi.nlm.nih.gov/pubmed/31722203
http://dx.doi.org/10.1016/j.celrep.2019.10.032
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author Gupta, Shubhranshu S.
Sharp, Robert
Hofferek, Colby
Kuai, Le
Dorn, Gerald W.
Wang, Jin
Chen, Min
author_facet Gupta, Shubhranshu S.
Sharp, Robert
Hofferek, Colby
Kuai, Le
Dorn, Gerald W.
Wang, Jin
Chen, Min
author_sort Gupta, Shubhranshu S.
collection PubMed
description 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.
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spelling pubmed-68867132019-12-03 NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8(+) T Cells Gupta, Shubhranshu S. Sharp, Robert Hofferek, Colby Kuai, Le Dorn, Gerald W. Wang, Jin Chen, Min Cell Rep Article 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. 2019-11-12 /pmc/articles/PMC6886713/ /pubmed/31722203 http://dx.doi.org/10.1016/j.celrep.2019.10.032 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Article
Gupta, Shubhranshu S.
Sharp, Robert
Hofferek, Colby
Kuai, Le
Dorn, Gerald W.
Wang, Jin
Chen, Min
NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8(+) T Cells
title NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8(+) T Cells
title_full NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8(+) T Cells
title_fullStr NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8(+) T Cells
title_full_unstemmed NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8(+) T Cells
title_short NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8(+) T Cells
title_sort nix-mediated mitophagy promotes effector memory formation in antigen-specific cd8(+) t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886713/
https://www.ncbi.nlm.nih.gov/pubmed/31722203
http://dx.doi.org/10.1016/j.celrep.2019.10.032
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