NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8+ T Cells
| العنوان: | NIX-Mediated Mitophagy Promotes Effector Memory Formation in Antigen-Specific CD8+ T Cells |
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| المؤلفون: | Jin Wang, Shubhranshu S. Gupta, Gerald W. Dorn, Le Kuai, Robert Sharp, Colby J. Hofferek, Min Chen |
| المصدر: | Cell reports Cell Reports, Vol 29, Iss 7, Pp 1862-1877.e7 (2019) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, CD8-Positive T-Lymphocytes, General Biochemistry, Genetics and Molecular Biology, Article, Mitochondrial Proteins, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Mitophagy, Cytotoxic T cell, Animals, lcsh:QH301-705.5, Beta oxidation, chemistry.chemical_classification, Mice, Knockout, Fatty acid metabolism, Chemistry, Effector, Autophagy, Fatty acid, Membrane Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, 3. Good health, Cell biology, 030104 developmental biology, lcsh:Biology (General), Immunologic Memory, 030217 neurology & neurosurgery, CD8 |
| الوصف: | SUMMARY 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. Graphical Abstract In Brief Gupta et al. demonstrate that mitophagy mediated by NIX, a mitochondrial outer membrane protein, plays a critical role in CD8+ T cell effector memory formation by regulating mitochondrial superoxide-dependent HIF1α protein accumulation and fatty acid metabolism. These findings elucidate the molecular mechanisms regulating T cell effector memory formation against viruses. |
| اللغة: | English |
| تدمد: | 2211-1247 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::141f58daf0a39634f7a5a58093db9ddcTest http://europepmc.org/articles/PMC6886713Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....141f58daf0a39634f7a5a58093db9ddc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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