PT - JOURNAL ARTICLE AU - Saskia Rödl AU - Fabian den Brave AU - Markus Räschle AU - Büsra Kizmaz AU - Svenja Lenhard AU - Carina Groh AU - Hanna Becker AU - Jannik Zimmermann AU - Bruce Morgan AU - Elke Richling AU - Thomas Becker AU - Johannes M Herrmann TI - The metabolite-controlled ubiquitin conjugase Ubc8 promotes mitochondrial protein import AID - 10.26508/lsa.202201526 DP - 2023 Jan 01 TA - Life Science Alliance PG - e202201526 VI - 6 IP - 1 4099 - https://www.life-science-alliance.org/content/6/1/e202201526.short 4100 - https://www.life-science-alliance.org/content/6/1/e202201526.full SO - Life Sci. Alliance2023 Jan 01; 6 AB - Mitochondria play a key role in cellular energy metabolism. Transitions between glycolytic and respiratory conditions induce considerable adaptations of the cellular proteome. These metabolism-dependent changes are particularly pronounced for the protein composition of mitochondria. Here, we show that the yeast cytosolic ubiquitin conjugase Ubc8 plays a crucial role in the remodeling process when cells transition from respiratory to fermentative conditions. Ubc8 is a conserved and well-studied component of the catabolite control system that is known to regulate the stability of gluconeogenic enzymes. Unexpectedly, we found that Ubc8 also promotes the assembly of the translocase of the outer membrane of mitochondria (TOM) and increases the levels of its cytosol-exposed receptor subunit Tom22. Ubc8 deficiency results in compromised protein import into mitochondria and reduced steady-state levels of mitochondrial proteins. Our observations show that Ubc8, which is controlled by the prevailing metabolic conditions, promotes the switch from glucose synthesis to glucose usage in the cytosol and induces the biogenesis of the mitochondrial TOM machinery to improve mitochondrial protein import during phases of metabolic transition.