Journal
EMBO JOURNAL
Volume 41, Issue 12, Pages -Publisher
WILEY
DOI: 10.15252/embj.2021109049
Keywords
immune cell infiltration; mitochondrial bioenergetics; oxidative phosphorylation; protein translation; transcription factor
Categories
Funding
- NIH [2P40OD010949-10A1, P40OD018537]
- City of Vienna through the Vienna Business Agency
- Austrian Science Fund (FWF) Lise Meitner Fellowship [M2379-B28]
- Austrian Science Fund (FWF) [ASI_FWF01_P29638S]
- NIH/NIGMS [R01GM111779-06, RO1GM135628-01]
- European Research Council (ERC) [677006]
- Natural Sciences and Engineering Research Council of Canada [RGPIN-2019-06766]
- [CIG 334077/IRTIM]
- European Research Council (ERC) [677006] Funding Source: European Research Council (ERC)
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A previously uncharacterized nuclear protein, Atossa, controls cellular metabolism to support macrophage invasion into the germband of Drosophila. Atossa increases mRNA levels of proteins and enzymes related to mitochondrial bioenergetics, while Porthos enhances the translational efficiency of specific mRNAs, including those affecting mitochondrial functions. This genetic program powers up OxPhos and energy production to promote the leading of macrophages into tissues.
Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-alpha-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors.
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