Longevity Regulation by Proline Oxidation in Yeast.

Proline is a pivotal and multifunctional amino acid that is used not only as a nitrogen source but also as a stress protectant and energy source. Therefore, proline metabolism is known to be important in maintaining cellular homeostasis. Here, we discovered that proline oxidation, catalyzed by the proline oxidase Put1, a mitochondrial flavin-dependent enzyme converting proline into ∆-pyrroline-5-carboxylate, controls the chronological lifespan of the yeast . Intriguingly, the yeast strain with deletion showed a reduced chronological lifespan compared with the wild-type strain. The addition of proline to the culture medium significantly increased the longevity of wild-type cells but not that of -deleted cells. We next found that induction of the transcriptional factor Put3-dependent and degradation of proline occur during the aging of yeast cells. Additionally, the lifespan of the -deleted strain, which is deficient in induction, was shorter than that of the wild-type strain. More importantly, the oxidation of proline by Put1 helped maintain the mitochondrial membrane potential and ATP production through the aging period. These results indicate that mitochondrial energy metabolism is maintained through oxidative degradation of proline and that this process is important in regulating the longevity of yeast cells.