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  A microscopy-based screen identifies cellular kinases modulating mitochondrial translation

Yousefi, R., Cruz-Zaragoza, L., Valpadashi, A., Hansohn, C., Dahal, D., Richter-Dennerlein, R., et al. (2025). A microscopy-based screen identifies cellular kinases modulating mitochondrial translation. Cell Reports, 44(1): 115143. doi:10.1016/j.celrep.2024.115143.

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1-s2.0-S2211124724014943-main.pdf (Publisher version), 7MB
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Yousefi, R., Author
Cruz-Zaragoza, L.D., Author
Valpadashi, A., Author
Hansohn, Carina1, Author           
Dahal, D., Author
Richter-Dennerlein, R., Author
Rizzoli, S., Author
Urlaub, H.1, Author           
Rehling, Peter2, Author           
Pacheu-Grau, D., Author
Affiliations:
1Research Group of Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350290              
2MPI-NAT Fellow Mitochondrial Biogenesis and Assembly of membrane Protein Complexes, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3505610              

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 Abstract: Mitochondrial DNA encodes 13 subunits of the oxidative phosphorylation (OXPHOS) system, which are synthesized inside the organelle and essential for cellular energy supply. How mitochondrial gene expression is regulated and integrated into cellular physiology is little understood. Here, we perform a high-throughput screen combining fluorescent labeling of mitochondrial translation products with small interfering RNA (siRNA)-mediated knockdown to identify cellular kinases regulating translation. As proof of principle, the screen identifies known kinases that affect mitochondrial translation, and it also reveals several kinases not yet linked to this process. Among the latter, we focus on the primarily cytosolic kinase, fructosamine 3 kinase (FN3K), which localizes partially to the mitochondria to support translation. FN3K interacts with the mitochondrial ribosome and modulates its assembly, thereby affecting translation. Overall, our work provides a reliable approach to identify protein functions for mitochondrial gene expression in a high-throughput manner.

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Language(s): eng - English
 Dates: 2024-12-312025-01-28
 Publication Status: Issued
 Pages: -
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 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.celrep.2024.115143
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Project name : ERCAdG
Grant ID : 101095062
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 44 (1) Sequence Number: 115143 Start / End Page: - Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247