Putative mitochondrial α-ketoglutarate-dependent dioxygenase Fmp12 controls utilization of proline as an energy source in .

The amino acid proline functions as a nitrogen source and as a stress protectant in the yeast . However, utilization of proline as a carbon source in cells has not been studied yet. In the process of study on the physiological roles of the found-in-mitochondrial-proteome () genes in proline metabolism, we found that Δ cells could grow better than wild-type cells on agar plate medium containing proline as the sole nitrogen and carbon sources. In contrast, overexpression of negatively affected cell growth under the same condition. The Fmp12 protein was localized in the mitochondria and was constitutively expressed. Deletion of the genes that encode mitochondrial enzymes, such as proline dehydrogenase (), Δ-pyrroline-5-carboxylate dehydrogenase (), alanine transaminase (), and α-ketoglutarate dehydrogenase subunit (), abolished the enhanced cell growth in Δ. These results provided the first evidence that proline can be utilized as a carbon source via the mitochondrial proline metabolic pathway and the subsequent tricarboxylic acid (TCA) cycle in . The function of Fmp12, which has a similarity with α-ketoglutarate-dependent dioxygenases of the yeast species and human, might inhibit cell growth by skipping the ATP production step of the TCA cycle.