Mark R. Lundquist
Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy
Lundquist, Mark R.; Goncalves, Marcus D.; Loughran, Ryan M.; Possik, Elite; Vijayaraghavan, Tarika; Yang, Annan; Pauli, Chantal; Ravi, Archna; Verma, Akanksha; Yang, Zhiwei; Johnson, Jared L.; Wong, Jenny C.Y.; Ma, Yilun; Hwang, Katie Seo-Kyoung; Weinkove, David; Divecha, Nullin; Asara, John M.; Elemento, Olivier; Rubin, Mark A.; Kimmelman, Alec C.; Pause, Arnim; Cantley, Lewis C.; Emerling, Brooke M.
Authors
Marcus D. Goncalves
Ryan M. Loughran
Elite Possik
Tarika Vijayaraghavan
Annan Yang
Chantal Pauli
Archna Ravi
Akanksha Verma
Zhiwei Yang
Jared L. Johnson
Jenny C.Y. Wong
Yilun Ma
Katie Seo-Kyoung Hwang
Professor David Weinkove david.weinkove@durham.ac.uk
Professor
Nullin Divecha
John M. Asara
Olivier Elemento
Mark A. Rubin
Alec C. Kimmelman
Arnim Pause
Lewis C. Cantley
Brooke M. Emerling
Abstract
While the majority of phosphatidylinositol-4, 5-bisphosphate (PI-4, 5-P2) in mammalian cells is generated by the conversion of phosphatidylinositol-4-phosphate (PI-4-P) to PI-4, 5-P2, a small fraction can be made by phosphorylating phosphatidylinositol-5-phosphate (PI-5-P). The physiological relevance of this second pathway is not clear. Here, we show that deletion of the genes encoding the two most active enzymes in this pathway, Pip4k2a and Pip4k2b, in the liver of mice causes a large enrichment in lipid droplets and in autophagic vesicles during fasting. These changes are due to a defect in the clearance of autophagosomes that halts autophagy and reduces the supply of nutrients salvaged through this pathway. Similar defects in autophagy are seen in nutrient-starved Pip4k2a−/−Pip4k2b−/− mouse embryonic fibroblasts and in C. elegans lacking the PI5P4K ortholog. These results suggest that this alternative pathway for PI-4, 5-P2 synthesis evolved, in part, to enhance the ability of multicellular organisms to survive starvation.
Citation
Lundquist, M. R., Goncalves, M. D., Loughran, R. M., Possik, E., Vijayaraghavan, T., Yang, A., Pauli, C., Ravi, A., Verma, A., Yang, Z., Johnson, J. L., Wong, J. C., Ma, Y., Hwang, K. S.-K., Weinkove, D., Divecha, N., Asara, J. M., Elemento, O., Rubin, M. A., Kimmelman, A. C., …Emerling, B. M. (2018). Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy. Molecular Cell, 70(3), 531-544.e9. https://doi.org/10.1016/j.molcel.2018.03.037
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 29, 2018 |
Online Publication Date | May 3, 2018 |
Publication Date | 2018-05 |
Deposit Date | May 4, 2018 |
Journal | Molecular Cell |
Print ISSN | 1097-2765 |
Publisher | Cell Press |
Peer Reviewed | Peer Reviewed |
Volume | 70 |
Issue | 3 |
Pages | 531-544.e9 |
DOI | https://doi.org/10.1016/j.molcel.2018.03.037 |
Public URL | https://durham-repository.worktribe.com/output/1327399 |
You might also like
Rapid measurement of ageing by automated monitoring of movement of C. elegans populations
(2023)
Journal Article
Imaging Fluorescent Nuclear Pore Complex Proteins in C. elegans
(2022)
Book Chapter
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search