![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
|
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
5MB | |
![[img]](http://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplemental Information)
56MB |
| Item Type: | Article |
|---|---|
| Title: | Autophagy-dependent generation of free fatty acids is critical for normal neutrophil differentiation |
| Creators Name: | Riffelmacher, T. and Clarke, A. and Richter, F.C. and Stranks, A. and Pandey, S. and Danielli, S. and Hublitz, P. and Yu, Z. and Johnson, E. and Schwerd, T. and McCullagh, J. and Uhlig, H. and Jacobsen, S.E.W. and Simon, A.K. |
| Abstract: | 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. |
| Keywords: | Autophagy, Neutrophil, Differentiation, Granulopoiesis, Energy Metabolism, Lipid Droplets, Lipophagy, Fatty Acid Oxidation, Animals, Mice |
| Source: | Immunity |
| ISSN: | 1074-7613 |
| Publisher: | Elsevier / Cell Press |
| Volume: | 47 |
| Number: | 3 |
| Page Range: | 466-480.e5 |
| Date: | 19 September 2017 |
| Official Publication: | https://doi.org/10.1016/j.immuni.2017.08.005 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
Download Statistics
Download Statistics
