Schatton, Desiree, Di Pietro, Giada, Szczepanowska, Karolina ORCID: 0000-0003-4689-2350, Veronese, Matteo, Marx, Marie-Charlotte, Braunoehler, Kristina, Barth, Esther, Mueller, Stefan, Giavalisco, Patrick, Langer, Thomas, Trifunovic, Aleksandra ORCID: 0000-0002-5472-3517 and Rugarli, Elena, I (2022). CLUH controls astrin-1 expression to couple mitochondrial metabolism to cell cycle progression. eLife, 11. CAMBRIDGE: eLIFE SCIENCES PUBL LTD. ISSN 2050-084X

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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 (clustered mitochondria homolog) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schatton, DesireeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Pietro, GiadaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szczepanowska, KarolinaUNSPECIFIEDorcid.org/0000-0003-4689-2350UNSPECIFIED
Veronese, MatteoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marx, Marie-CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braunoehler, KristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barth, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giavalisco, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trifunovic, AleksandraUNSPECIFIEDorcid.org/0000-0002-5472-3517UNSPECIFIED
Rugarli, Elena, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-669554
DOI: 10.7554/eLife.74552
Journal or Publication Title: eLife
Volume: 11
Date: 2022
Publisher: eLIFE SCIENCES PUBL LTD
Place of Publication: CAMBRIDGE
ISSN: 2050-084X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OPEN READING FRAMES; MASS-SPECTROMETRY; COMPUTATIONAL PLATFORM; PROTEIN ASTRIN; MTORC1; CANCER; SPAG5; PROLIFERATION; TRANSLATION; BIOGENESISMultiple languages
BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/66955

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