CLUH controls astrin-1 expression to couple mitochondrial metabolism to cell cycle progression
- University of Cologne, Germany
- Max Planck Institute for Biology of Ageing, Germany
Abstract
Proliferating cells undergo metabolic changes in synchrony with cell cycle progression and cell division. Mitochondria provide fuel, metabolites, and ATP during different phases of the cell cycle, however it is not completely understood how mitochondrial function and the cell cycle are coordinated. CLUH is a post-transcriptional regulator of mRNAs encoding mitochondrial proteins involved in oxidative phosphorylation and several metabolic pathways. Here, we show a role of CLUH in regulating the expression of astrin, which is involved in metaphase to anaphase progression, centrosome integrity, and mTORC1 inhibition. We find that CLUH binds both the SPAG5 mRNA and its product astrin, and controls the synthesis and the stability of the full-length astrin-1 isoform. We show that CLUH interacts with astrin-1 specifically during interphase. Astrin-depleted cells show mTORC1 hyperactivation and enhanced anabolism. On the other hand, cells lacking CLUH show decreased astrin levels and increased mTORC1 signaling, but cannot sustain anaplerotic and anabolic pathways. In absence of CLUH, cells fail to grow during G1, and progress faster through the cell cycle, indicating dysregulated matching of growth, metabolism and cell cycling. Our data reveal a role of CLUH in coupling growth signaling pathways and mitochondrial metabolism with cell cycle progression.
Data availability
Source data files have been provided for Figures 1, 2, 3, 4, 5, 6 and 7.The mass spectrometry proteomic data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers: PXD029142, PXD029145, PXD029156.
Article and author information
Author details
Patrick Giavalisco
Aleksandra Trifunovic
Funding
Deutsche Forschungsgemeinschaft (269925409)
- Elena I Rugarli
Deutsche Forschungsgemeinschaft (411422114-GRK 2550)
- Elena I Rugarli
Max Planck Institute for Biology of Ageing (open access funding)
- Thomas Langer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Erica A Golemis, Fox Chase Cancer Center, United States
Version history
- Received: October 8, 2021
- Preprint posted: April 26, 2022 (view preprint)
- Accepted: May 12, 2022
- Accepted Manuscript published: May 13, 2022 (version 1)
- Version of Record published: May 26, 2022 (version 2)
Copyright
© 2022, Schatton et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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CLUH controls astrin-1 expression to couple mitochondrial metabolism to cell cycle progression
eLife 11:e74552.
https://doi.org/10.7554/eLife.74552
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