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  Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation

Puleston, D. J., Buck, M. D., Geltink, R. I. K., Kyle, R. L., Caputa, G., O’Sullivan, D., et al. (2019). Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation. Cell Metabolism, 30, 1-12. doi:org/10.1016/j.cmet.2019.05.003.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-A643-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-A644-4
Genre: Journal Article

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 Creators:
Puleston, Daniel J.1, Author
Buck, Michael D.1, Author
Geltink, Ramon I. Klein1, Author
Kyle, Ryan L.1, Author
Caputa, George1, Author
O’Sullivan, David1, Author
Cameron, Alanna M.1, Author
Castoldi, Angela1, Author
Musa, Yaarub1, Author
Kabat, Agnieszka M.1, Author
Zhang, Ying2, Author
Flachsmann, Lea J.1, Author
Field, Cameron S.1, Author
Patterson, Annette E.1, Author
Scherer, Stefanie2, Author
Alfei, Francesca2, Author
Baixauli, Francesc1, Author
Austin, S. Kyle1, Author
Kelly, Beth1, Author
Matsushita, Mai1, Author
Curtis, Jonathan D.1, AuthorGrzes, Katarzyna M.1, AuthorVilla, Matteo1, AuthorCorrado, Mauro1, AuthorSanin, David E.1, AuthorQiu, Jing1, AuthorPällman, Nora2, AuthorPaz, Katelyn2, AuthorMaccari, Maria Elena2, AuthorBlazar, Bruce R.2, AuthorMittler, Gerhard1, AuthorBuescher, Joerg M.1, AuthorZehn, Dietmar2, AuthorRospert, Sabine2, AuthorPearce, Edward J.1, AuthorBalabanov, Stefan2, AuthorPearce, Erika L.1, Author more..
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
2External Organizations, ou_persistent22              

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 Abstract: How cells adapt metabolism to meet demands is an active area of interest across biology. Among a broad range of functions, the polyamine spermidine is needed to hypusinate the translation factor eukaryotic initiation factor 5A (eIF5A). We show here that hypusinated eIF5A (eIF5AH) promotes the efficient expression of a subset of mitochondrial proteins involved in the TCA cycle and oxidative phosphorylation (OXPHOS). Several of these proteins have mitochondrial targeting sequences (MTSs) that in part confer an increased dependency on eIF5AH. In macrophages, metabolic switching between OXPHOS and glycolysis supports divergent functional fates stimulated by activation signals. In these cells, hypusination of eIF5A appears to be dynamically regulated after activation. Using in vivo and in vitro models, we show that acute inhibition of this pathway blunts OXPHOS-dependent alternative activation, while leaving aerobic glycolysis-dependent classical activation intact. These results might have implications for therapeutically controlling macrophage activation by targeting the polyamine-eIF5A-hypusine axis.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: org/10.1016/j.cmet.2019.05.003
 Degree: -

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Title: Cell Metabolism
  Alternative Title : Cell Metabolism
Source Genre: Journal
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Publ. Info: Cambridge, MA : Cell Press
Pages: - Volume / Issue: 30 Sequence Number: - Start / End Page: 1 - 12 Identifier: ISSN: 1550-4131
CoNE: https://pure.mpg.de/cone/journals/resource/111088195284928