Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila.

Autor: Emtenani S; Institute of Science and Technology Austria, Klosterneuburg, Austria., Martin ET; Department of Biological Sciences, RNA Institute, University at Albany, Albany, NY, USA., Gyoergy A; Institute of Science and Technology Austria, Klosterneuburg, Austria., Bicher J; Institute of Science and Technology Austria, Klosterneuburg, Austria., Genger JW; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Köcher T; Vienna BioCenter Core Facilities, Vienna, Austria., Akhmanova M; Institute of Science and Technology Austria, Klosterneuburg, Austria., Guarda M; Institute of Science and Technology Austria, Klosterneuburg, Austria., Roblek M; Institute of Science and Technology Austria, Klosterneuburg, Austria., Bergthaler A; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Hurd TR; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Rangan P; Department of Biological Sciences, RNA Institute, University at Albany, Albany, NY, USA., Siekhaus DE; Institute of Science and Technology Austria, Klosterneuburg, Austria.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2022 Jun 14; Vol. 41 (12), pp. e109049. Date of Electronic Publication: 2022 Mar 23.
DOI: 10.15252/embj.2021109049
Abstrakt: 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-α-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.
(© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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