Metabolic adaptation to changing demands underlies homeostasis. During inflammation or metastasis, cells leading migration into challenging environments require an energy boost, however what controls this capacity is unknown. We identify a previously unstudied nuclear protein, Atossa, as changing metabolism in Drosophila melanogaster immune cells to promote tissue invasion. Atossa’s vertebrate orthologs, FAM214A-B, can fully substitute for Atossa, indicating functional conservation from flies to mammals. Atossa increases mRNA levels of Porthos, an unstudied RNA helicase and two metabolic enzymes, LKR/SDH and GR/HPR. Porthos increases translation of a gene subset, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Respiration measurements and metabolomics indicate that Atossa and Porthos powers up mitochondrial oxidative phosphorylation to produce sufficient energy for leading macrophages to forge a path into tissues. As increasing oxidative phosphorylation enables many crucial physiological responses, this unique genetic program may modulate a wide range of cellular behaviors beyond migration.
We thank: The Drosophila Genomics Resource Center supported by NIH grant 2P40OD010949-10A1 for plasmids, the Bloomington Drosophila Stock Center supported by NIH grant P40OD018537 and the Vienna Drosophila Resource Center (Dietzl et al., 2007) for fly stocks, FlyBase (Thurmond et al., 2019) for essential genomic information, and the BDGP in situ database for data (Tomancak et al., 2002; Tomancak et al., 2007). We thank the Vienna BioCenter Core Facilities for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria for technical support and assistance with microscopy and FACS analysis. We thank C. Guet, C. Navarro and Siekhaus group members for discussions and comments on the manuscript. D.E.S. was funded by Marie Curie CIG 334077/IRTIM and Austrian Science Fund (FWF) grant ASI_FWF01_P29638S, P.R. by NIH/NIGMS (R01GM111779-06 and RO1GM135628-01), and A.B. with support of the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, grant no. 677006, ‘‘CMIL’’. T.R.H. is supported by the Natural Sciences and Engineering Research Council of Canada (RGPIN-2019-06766).
Emtenani S, Martin ET, György A, et al. A genetic program boosts mitochondrial function to power macrophage tissue invasion. bioRxiv. doi:10.1101/2021.02.18.431643
Emtenani, S., Martin, E. T., György, A., Bicher, J., Genger, J.-W., Hurd, T. R., … Siekhaus, D. E. (n.d.). A genetic program boosts mitochondrial function to power macrophage tissue invasion. bioRxiv. https://doi.org/10.1101/2021.02.18.431643
Emtenani, Shamsi, Elliott T. Martin, Attila György, Julia Bicher, Jakob-Wendelin Genger, Thomas R. Hurd, Thomas Köcher, Andreas Bergthaler, Prashanth Rangan, and Daria E Siekhaus. “A Genetic Program Boosts Mitochondrial Function to Power Macrophage Tissue Invasion.” BioRxiv, n.d. https://doi.org/10.1101/2021.02.18.431643.
S. Emtenani et al., “A genetic program boosts mitochondrial function to power macrophage tissue invasion,” bioRxiv. .
Emtenani S, Martin ET, György A, Bicher J, Genger J-W, Hurd TR, Köcher T, Bergthaler A, Rangan P, Siekhaus DE. A genetic program boosts mitochondrial function to power macrophage tissue invasion. bioRxiv, 10.1101/2021.02.18.431643.
Emtenani, Shamsi, et al. “A Genetic Program Boosts Mitochondrial Function to Power Macrophage Tissue Invasion.” BioRxiv, doi:10.1101/2021.02.18.431643.