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urn:hdl:2445/152738 Sensing of nutrients by CPT1C regulates late endosome/lysosome anterograde transport and axon growth Palomo-Guerrero, Marta Fadó Andrés, Rut Casas, Maria Pérez-Montero, Marta Baena Muñoz, Miguel Helmer, Patrick O Domínguez, José Luis Roig, Aina Serra i Cucurull, Dolors Hayen, Heiko Stenmark, Harald Raiborg, Camilla Casals, Núria Carnitina palmitoïl-transferasa 1 Axons Lisosomes Carnitine palmitoyltransferase I Axons Lysosomes Anterograde transport of late endosomes or lysosomes (LE/Lys) is crucial for proper axon growth. However, the role of energetic nutrients has been poorly explored. Malonyl-CoA is a precursor of fatty acids, and its intracellular levels highly fluctuate depending on glucose availability or the energy sensor AMP-activated protein kinase (AMPK). We demonstrate in HeLa cells that carnitine palmitoyltransferase 1C (CPT1C) senses malonyl-CoA and enhances LE/Lys anterograde transport by interacting with the endoplasmic reticulum protein protrudin and facilitating the transfer of Kinesin-1 from protrudin to LE/Lys. In cultured mouse cortical neurons, glucose deprivation, pharmacological activation of AMPK or inhibition of malonyl-CoA synthesis decreases LE/Lys abundance at the axon terminal, and shortens axon length in a CPT1C-dependent manner. These results identify CPT1C as a new regulator of anterograde LE/Lys transport in response to malonyl-CoA changes, and give insight into how axon growth is controlled by nutrients. 2020-03-13T12:01:36Z 2020-03-13T12:01:36Z 2019-12-23 2020-03-13T12:01:37Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.7554/eLife.51063 eLife, 2019, vol. 8, p. e51063 https://doi.org/10.7554/eLife.51063 info:eu-repo/grantAgreement/EC/H2020/788954/EU//CODE cc-by (c) Palomo-Guerrero, Marta et al., 2019 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess eLife Sciences Articles publicats en revistes (Bioquímica i Fisiologia)