An antioxidative mechanism mediated by the yeast N-acetyltransferase Mpr1: oxidative stress-induced arginine synthesis and its physiological role.
Saccharomyces cerevisiaeSigma1278b has the MPR1 gene encoding the N-acetyltransferase Mpr1 that acetylates the proline metabolism intermediate Delta(1)-pyrroline-5-carboxylate (P5C)/glutamate-gamma-semialdehyde (GSA) in vitro. In addition, Mpr1 protects cells from various oxidative stresses by regulating the levels of intracellular reactive oxygen species (ROS). However, the relationship between P5C/GSA acetylation and antioxidative mechanism involving Mpr1 remains unclear. Here, we report the synthesis of oxidative stress-induced arginine via P5C/GSA acetylation catalyzed by Mpr1. Gene disruption analysis revealed that Mpr1 converts P5C/GSA into N-acetyl-GSA for arginine synthesis in the mitochondria, indicating that Mpr1 mediates the proline and arginine metabolic pathways. More importantly, Mpr1 regulate ROS generation by acetylating toxic P5C/GSA. Under oxidative stress conditions, the transcription of PUT1 encoding the proline oxidase Put1 and MPR1 was strongly induced, and consequently, the arginine content was significantly increased. We also found that two deletion mutants (Deltampr1/2 and Deltaput1) were more sensitive to high-temperature stress than the wild-type strain, but that direct treatment with arginine restored the cell viability of these mutants. These results suggest that Mpr1-dependent arginine synthesis confers stress tolerance. We propose an antioxidative mechanism that is involved in stress-induced arginine synthesis requiring Mpr1 and Put1.
Nishimura
Akira
A
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan.
Kotani
Tetsuya
T
Sasano
Yu
Y
Takagi
Hiroshi
H
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000096:biosynthesis*; D055786:Gene Knockout Techniques; D005971:Glutamates / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D050296:Microbial Viability; D008954:Models, Biological; D016254:Mutagenesis, Insertional; D018384:Oxidative Stress; D011394:Proline Oxidase / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D013696:Temperature
D005971:Glutamates; D011758:Pyrroles; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C015485:delta-1-pyrroline-5-carboxylate; C021199:glutamic acid gamma-semialdehyde; D001120:Arginine; D011394:Proline Oxidase; D000123:Acetyltransferases; C492447:Mpr1 protein, S cerevisiae