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Smaug1 membrane-less organelles respond to AMPK and mTOR and affect mitochondrial function

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dc.contributor.authorFernández-Alvarez, Ana J.
dc.contributor.authorGabriela Thomas, María
dc.contributor.authorPascual, Malena L.
dc.contributor.authorHabif, Martín
dc.contributor.authorPimentel, Jerónimo
dc.contributor.authorCorbat, Agustín A.
dc.contributor.authorPessoa, João
dc.contributor.authorLa Spina, Pablo E.
dc.contributor.authorBoscaglia, Lara
dc.contributor.authorPlessis, Anne
dc.contributor.authorCarmo-Fonseca, Maria
dc.contributor.authorGrecco, Hernán E.
dc.contributor.authorCasado, Marta
dc.contributor.authorBoccaccio, Graciela L.
dc.date.accessioned2022-08-03T16:16:58Z
dc.date.available2022-08-03T16:16:58Z
dc.date.issued2022
dc.description© 2022 Published by The Company of Biologists Ltd.pt_PT
dc.description.abstractSmaug is a conserved translational regulator that binds numerous mRNAs, including nuclear transcripts that encode mitochondrial enzymes. Smaug orthologs form cytosolic membrane-less organelles (MLOs) in several organisms and cell types. We have performed single-molecule fluorescence in situ hybridization (FISH) assays that revealed that SDHB and UQCRC1 mRNAs associate with Smaug1 bodies in U2OS cells. Loss of function of Smaug1 and Smaug2 (also known as SAMD4A and SAMD4B, respectively) affected both mitochondrial respiration and morphology of the mitochondrial network. Phenotype rescue by Smaug1 transfection depends on the presence of its RNA-binding domain. Moreover, we identified specific Smaug1 domains involved in MLO formation, and found that impaired Smaug1 MLO condensation correlates with mitochondrial defects. Mitochondrial complex I inhibition upon exposure to rotenone, but not strong mitochondrial uncoupling upon exposure to CCCP, rapidly induced the dissolution of Smaug1 MLOs. Metformin and rapamycin elicited similar effects, which were blocked by pharmacological inhibition of AMP-activated protein kinase (AMPK). Finally, we found that Smaug1 MLO dissolution weakens the interaction with target mRNAs, thus enabling their release. We propose that mitochondrial respiration and the AMPK-mTOR balance controls the condensation and dissolution of Smaug1 MLOs, thus regulating nuclear mRNAs that encode key mitochondrial proteins. This article has an associated First Person interview with the first authors of the paper.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Cell Sci. 2022 Dec 1;135(1):jcs253591pt_PT
dc.identifier.doi10.1242/jcs.253591pt_PT
dc.identifier.eissn1477-9137
dc.identifier.issn0021-9533
dc.identifier.urihttp://hdl.handle.net/10451/54050
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherThe Company of Biologistspt_PT
dc.relation.publisherversionhttps://journals.biologists.com/jcspt_PT
dc.subjectAMPKpt_PT
dc.subjectMembrane-less organellespt_PT
dc.subjectMetforminpt_PT
dc.subjectMitochondriapt_PT
dc.subjectProcessing bodiespt_PT
dc.subjectSmaugpt_PT
dc.subjectUQCRC1pt_PT
dc.titleSmaug1 membrane-less organelles respond to AMPK and mTOR and affect mitochondrial functionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.titleJournal of Cell Sciencept_PT
oaire.citation.volume135pt_PT
person.familyNamePessoa
person.familyNameCarmo-Fonseca
person.givenNameJoão
person.givenNameMaria
person.identifier.ciencia-idB31F-0435-0753
person.identifier.orcid0000-0002-9202-5728
person.identifier.orcid0000-0002-3402-7143
person.identifier.scopus-author-id7007128195
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationd0d2427d-a306-4c97-98dc-0b7a0edce53d
relation.isAuthorOfPublicationf4cae50c-2389-4b6a-8e3a-8fd8e538add0
relation.isAuthorOfPublication.latestForDiscoveryd0d2427d-a306-4c97-98dc-0b7a0edce53d

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