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http://hdl.handle.net/10397/82233
| Title: | Rewiring neuronal glycerolipid metabolism determines the extent of axon regeneration | Authors: | Yang, C Wang, X Wang, JY Wang, XJ Chen, WT Lu, N Siniossoglou, S Yao, ZP Liu, K |
Issue Date: | 2020 | Source: | Neuron, 22 Jan. 2020, v. 105, no. 2, p. 276-292 | Abstract: | How adult neurons coordinate lipid metabolism to regenerate axons remains elusive. We found that depleting neuronal lipin1, a key enzyme controlling the balanced synthesis of glycerolipids through the glycerol phosphate pathway, enhanced axon regeneration after optic nerve injury. Axotomy elevated lipin1 in retinal ganglion cells, which contributed to regeneration failure in the CNS by favorably producing triglyceride (TG) storage lipids rather than phospholipid (PL) membrane lipids in neurons. Regrowth induced by lipin1 depletion required TG hydrolysis and PL synthesis. Decreasing TG synthesis by deleting neuronal diglyceride acyltransferases (DGATs) and enhancing PL synthesis through the Kennedy pathway promoted axon regeneration. In addition, peripheral neurons adopted this mechanism for their spontaneous axon regeneration. Our study reveals a critical role of lipin1 and DGATs as intrinsic regulators of glycerolipid metabolism in neurons and indicates that directing neuronal lipid synthesis away from TG synthesis and toward PL synthesis may promote axon regeneration. | Publisher: | Cell Press | Journal: | Neuron | ISSN: | 0896-6273 | EISSN: | 1097-4199 | DOI: | 10.1016/j.neuron.2019.10.009 | Rights: | ©2019 The Author(s). Published by Elsevier Inc.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). The following publication Yang, C., Wang, X., Wang, J. Y., Wang, X. J., Chen, W. T., Lu, N., ... & Liu, K. (2020). Rewiring neuronal glycerolipid metabolism determines the extent of axon regeneration. Neuron, 105(2), 276-292 is available at https://dx.doi.org/10.1016/j.neuron.2019.10.009 |
| Appears in Collections: | Journal/Magazine Article |
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