Smaug membraneless organelles regulate mitochondrial function

Fernandez-Alvarez, A. J.; Thomas, M. G.; Pascual, M. L.; Habif, M.; Pimentel, J.; Corbat, A. A.; Pessoa, J. P.; La Spina, P. E.; Boscaglia, L.; Plessis, A.; Carmo-Fonseca, M.; Grecco, H. E.; Casado, M.; Boccaccio, G. L.

doi:10.1101/2020.07.31.223099

bioRxiv · 10.1101/2020.07.31.223099

Smaug membraneless organelles regulate mitochondrial function

Fernandez-Alvarez, A. J.·Thomas, M. G.·Pascual, M. L.·Habif, M.·Pimentel, J.·Corbat, A. A.·Pessoa, J. P.·La Spina, P. E.·Boscaglia, L.·Plessis, A.·Carmo-Fonseca, M.·Grecco, H. E.·Casado, M.·Boccaccio, G. L.

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Abstract

Smaug is a conserved translational repressor that recognizes specific RNA motifs in a large number of mRNAs, including nuclear transcripts that encode mitochondrial enzymes. Smaug orthologs have been shown to form membraneless organelles (MLOs) in several organisms and cell types. Using single-molecule FISH we show here that SDHB and UQCRC1 mRNAs associate with Smaug1 MLOs in the human cell line U2OS. Simultaneous loss of function of Smaug1 and Smaug2 affects both mitochondrial respiration and mitochondrial network morphology. Deletion of specific Smaug1 protein regions resulted in impaired MLO formation that correlates with mitochondrial defects. In addition, rotenone but not the respiratory chain uncoupling agent CCCP rapidly induces Smaug1 MLO dissolution. Finally, metformin elicits a similar effect on Smaug1 MLOs and provokes the release of bounded mRNAs. We propose that mitochondrial activity affects Smaug1 MLO dynamics, thus allowing for regulation of nuclear mRNAs that encode key mitochondrial proteins.

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Fernandez-Alvarez, A. J., Thomas, M. G., Pascual, M. L., Habif, M., Pimentel, J., Corbat, A. A., Pessoa, J. P., La Spina, P. E., Boscaglia, L., Plessis, A., Carmo-Fonseca, M., Grecco, H. E., Casado, M., Boccaccio, G. L.. 2020-07-31. Smaug membraneless organelles regulate mitochondrial function. https://doi.org/10.1101/2020.07.31.223099

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