Orthologues of the post-transcriptional regulator Smaug bind various mRNAs. In both insects and vertebrates, Smaug has been found to form membrane-less organelles (MLOs), termed Smaug bodies, which contain repressed mRNAs. Disruption of Smaug leads to various phenotypes in the mouse and fly, but the consequences of Smaug body formation remain poorly understood. Previous work in Drosophila hasshown that mRNAs encoding mitochondrial enzymes bind Smaug. Here, Graciela Boccaccio and colleagues (Fernández-Alvarez et al., 2022) investigate the role of Smaug1 and Smaug2 MLOs in mitochondrial function. Using single-molecule fluorescence in situ hybridisation (FISH), the authors reveal that succinate dehydrogenase subunit B (SDHB) and ubiquinol-cytochrome c reductase core protein (UQCRC1) mRNAs associate with Smaug bodies in U2OS cells. Knocking down Smaug1 and Smaug2 compromised mitochondrial complex I and II activities and led to increased mitochondrial fragmentation. Furthermore, the authors found that specific Smaug1 domains were necessary for the successful formation of MLOs, and that impaired Smaug1 MLO condensation led to mitochondrial defects. Pharmacological inhibition of complex I resulted in the dissolution of Smaug1 from MLOs and release of the two mitochondrial mRNAs from the Smaug body. Interestingly, the effects induced by these drugs were blocked by inhibiting AMPK. These findings indicate that mitochondrial respiration and AMPK-mTOR signalling balance the condensation and dissolution of Smaug1 MLOs, and regulate the release of nuclear mRNAs encoding mitochondrial enzymes.
