Unknown

Dataset Information

0

Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation.


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.

SUBMITTER: Puleston DJ 

PROVIDER: S-EPMC6688828 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation.

Puleston Daniel J DJ   Buck Michael D MD   Klein Geltink Ramon I RI   Kyle Ryan L RL   Caputa George G   O'Sullivan David D   Cameron Alanna M AM   Castoldi Angela A   Musa Yaarub Y   Kabat Agnieszka M AM   Zhang Ying Y   Flachsmann Lea J LJ   Field Cameron S CS   Patterson Annette E AE   Scherer Stefanie S   Alfei Francesca F   Baixauli Francesc F   Austin S Kyle SK   Kelly Beth B   Matsushita Mai M   Curtis Jonathan D JD   Grzes Katarzyna M KM   Villa Matteo M   Corrado Mauro M   Sanin David E DE   Qiu Jing J   Pällman Nora N   Paz Katelyn K   Maccari Maria Elena ME   Blazar Bruce R BR   Mittler Gerhard G   Buescher Joerg M JM   Zehn Dietmar D   Rospert Sabine S   Pearce Edward J EJ   Balabanov Stefan S   Pearce Erika L EL  

Cell metabolism 20190523 2


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<sup>H</sup>) 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  ...[more]

Similar Datasets

2019-05-24 | PXD013443 | Pride
| S-EPMC9441050 | biostudies-literature
| S-EPMC6863385 | biostudies-literature
| S-EPMC10146511 | biostudies-literature
| S-EPMC11358140 | biostudies-literature
| S-EPMC5328152 | biostudies-literature
2024-03-31 | GSE244063 | GEO
| S-EPMC9440896 | biostudies-literature
| S-EPMC7729396 | biostudies-literature
| S-EPMC7969969 | biostudies-literature