Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and 
Macrophage Activation

Puleston, Daniel J.; Buck, Michael D.; Geltink, Ramon I. Klein; Kyle, Ryan L.; Caputa, George; O’Sullivan, David; Cameron, Alanna M.; Castoldi, Angela; Musa, Yaarub; Kabat, Agnieszka M.; Zhang, Ying; Flachsmann, Lea J.; Field, Cameron S.; Patterson, Annette E.; Scherer, Stefanie; Alfei, Francesca; Baixauli, Francesc; Austin, S. Kyle; Kelly, Beth; Matsushita, Mai; Curtis, Jonathan D.; Grzes, Katarzyna M.; Villa, Matteo; Corrado, Mauro; Sanin, David E.; Qiu, Jing; Pällman, Nora; Paz, Katelyn; Maccari, Maria Elena; Blazar, Bruce R.; Mittler, Gerhard; Büscher, Jörg; Zehn, Dietmar; Rospert, Sabine; Pearce, Edward Jonathen; Balabanov, Stefan; Pearce, Erika Laine

doi:org/10.1016/j.cmet.2019.05.003

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Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation

MPG-Autoren

Puleston, Daniel J.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Buck, Michael D.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Geltink, Ramon I. Klein
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kyle, Ryan L.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Caputa, George
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

O’Sullivan, David
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Cameron, Alanna M.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Castoldi, Angela
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Musa, Yaarub
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kabat, Agnieszka M.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Flachsmann, Lea J.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Field, Cameron S.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Patterson, Annette E.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Baixauli, Francesc
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Austin, S. Kyle
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kelly, Beth
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Matsushita, Mai
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Curtis, Jonathan D.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Grzes, Katarzyna M.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Villa, Matteo
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201354

Corrado, Mauro
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sanin, David E.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Qiu, Jing
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons191219

Mittler, Gerhard
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons241896

Büscher, Jörg
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201435

Pearce, Edward Jonathen
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201431

Pearce, Erika Laine
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S1550413119302438?via%3Dihub
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Zitation

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.

Zitierlink: https://hdl.handle.net/21.11116/0000-0004-A643-5

Zusammenfassung

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 (eIF5A^H) 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.