Pla-Martin, David, Schatton, Desiree, Wiederstein, Janica L., Marx, Marie-Charlotte, Khiati, Salim, Krueger, Marcus and Rugarli, Elena, I (2020). CLUH granules coordinate translation of mitochondrial proteins with mTORC1 signaling and mitophagy. Embo J., 39 (9). HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

Mitochondria house anabolic and catabolic processes that must be balanced and adjusted to meet cellular demands. The RNA-binding protein CLUH (clustered mitochondria homolog) binds mRNAs of nuclear-encoded mitochondrial proteins and is highly expressed in the liver, where it regulates metabolic plasticity. Here, we show that in primary hepatocytes, CLUH coalesces in specific ribonucleoprotein particles that define the translational fate of target mRNAs, such as Pcx, Hadha, and Hmgcs2, to match nutrient availability. Moreover, CLUH granules play signaling roles, by recruiting mTOR kinase and the RNA-binding proteins G3BP1 and G3BP2. Upon starvation, CLUH regulates translation of Hmgcs2, involved in ketogenesis, inhibits mTORC1 activation and mitochondrial anabolic pathways, and promotes mitochondrial turnover, thus allowing efficient reprograming of metabolic function. In the absence of CLUH, a mitophagy block causes mitochondrial clustering that is rescued by rapamycin treatment or depletion of G3BP1 and G3BP2. Our data demonstrate that metabolic adaptation of liver mitochondria to nutrient availability depends on a compartmentalized CLUH-dependent post-transcriptional mechanism that controls both mTORC1 and G3BP signaling and ensures survival.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pla-Martin, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schatton, DesireeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiederstein, Janica L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marx, Marie-CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khiati, SalimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rugarli, Elena, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-334413
DOI: 10.15252/embj.2019102731
Journal or Publication Title: Embo J.
Volume: 39
Number: 9
Date: 2020
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
REGULATES MITOPHAGY; STRESS GRANULES; MESSENGER-RNAS; DEGRADATION; AUTOPHAGY; STARVATION; CLUELESS; PINK1; TORC1; COLOCALIZATIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33441

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