Fig. 9

Models for lipoylation mechanisms. a Lipoylation in yeast strains expressing suppressor constructs (mitochondrially targeted LplA or Fam1/Faa2) under supplementation conditions. Left: After LA has passed through the mitochondrial membranes, LplA activates it with AMP and transfers the lipoyl moiety onto Lat1, which is used as a substrate by Lip3 for Kgd2-lipoylation. Right: After entering mitochondria, C8 is activated by Fam1-1, possibly by direct attachment to ACP. Octanoyl-ACP serves as a substrate for Lip2 and the C8 is transferred onto Gcv3. Lip5 and Lip3 use octanoyl-Gcv3 for attachment of thiol groups and as a substrate for transfer to the PDH and KGD-complexes, respectively. b Lipoylation events under native conditions. Lip2 transfers C8 from Acp1 to Gcv3 and Lip5 adds the thiol groups to carbons 6 and 8, forming LA. Lip3 transfers the LA moiety onto Lat1 and Kgd2. The novelty of this model, based on the data presented here, is that Lip3 can also transfer LA from Lat1 to Kgd2. We postulate that this may serve as an additional layer of regulation to match the prevailing energy flux in the cell with PDH and KGD-complex activities. This activity of Lip3 could serve to quickly fine-tune the relative activities of PDH and KGD by simple transfer of the lipoyl moiety from Lat1 to Kgd2, for example in glucose-deprived conditions where the need for PDH-complex activity is reduced