The metabolite-controlled ubiquitin conjugase Ubc8 promotes mitochondrial protein import by enhancing assembly of the TOM complex

ABSTRACT: Mitochondria are essential organelles that play a key role in energy metabolism. Transitions between glycolytic and respiring 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 ubiquitin conjugase Ubc8 of the yeast cytosol plays a crucial role in the remodeling process when cells are shifted 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 gluconeogenesis enzymes. Unexpectedly, we found that Ubc8 also promotes the assembly of the translocase of the outer membrane of mitochondria (TOM) and stabilizes its cytosol-exposed receptor subunit Tom22. Ubc8 deficiency results in a compromised protein import into mitochondria and a subsequent accumulation of mitochondrial precursor proteins in the cytosol. Our observations show that Ubc8 which is controlled by the prevalent metabolic conditions, promotes on the one hand the switch from glucose synthesis to glucose usage in the cytosol and, on the other hand, the biogenesis of the mitochondrial TOM machinery in order to protect the mitochondrial import machinery during phases of metabolic transition.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

TISSUE(S): Cell Culture

SUBMITTER: Markus Räschle  

LAB HEAD: Markus Räschle

PROVIDER: PXD033171 | Pride | 2022-10-15

REPOSITORIES: Pride