Autophagy-dependent generation of free fatty acids is critical for normal neutrophil differentiation
| العنوان: | Autophagy-dependent generation of free fatty acids is critical for normal neutrophil differentiation |
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| المؤلفون: | Thomas Riffelmacher, Alexander Clarke, Felix C. Richter, Amanda Stranks, Sumeet Pandey, Sara Danielli, Philip Hublitz, Zhanru Yu, Errin Johnson, Tobias Schwerd, James McCullagh, Holm Uhlig, Sten Eirik W. Jacobsen, Anna Katharina Simon |
| المصدر: | Immunity |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Myelopoiesis, Neutrophils, Gene Expression Profiling, Lipolysis, Adaptation, Biological, Cell Differentiation, Fatty Acids, Nonesterified, Lipid Metabolism, Gene Knockout Techniques, Glucose, Pyruvic Acid, Autophagy, Animals, Cluster Analysis, Energy Metabolism, Oxidation-Reduction |
| الوصف: | Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive. Here, we have shown that metabolism and autophagy are developmentally programmed and essential for neutrophil differentiation in vivo. Atg7-deficient neutrophil precursors had increased glycolytic activity but impaired mitochondrial respiration, decreased ATP production, and accumulated lipid droplets. Inhibiting autophagy-mediated lipid degradation or fatty acid oxidation alone was sufficient to cause defective differentiation, while administration of fatty acids or pyruvate for mitochondrial respiration rescued differentiation in autophagy-deficient neutrophil precursors. Together, we show that autophagy-mediated lipolysis provides free fatty acids to support a mitochondrial respiration pathway essential to neutrophil differentiation. |
| تدمد: | 1097-4180 1074-7613 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::93027506ca0941db1eb4b2f6a14134be http://ora.ox.ac.uk/objects/uuid: |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.pmid.dedup....93027506ca0941db1eb4b2f6a14134be |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974180 10747613 |
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