The proline metabolism intermediate Δ1-pyrroline-5-carboxylate directly inhibits the mitochondrial respiration in budding yeast.
The proline metabolism intermediate Δ(1)-pyrroline-5-carboxylate (P5C) induces cell death in animals, plants and yeasts. To elucidate how P5C triggers cell death, we analyzed P5C metabolism, mitochondrial respiration and superoxide anion generation in the yeast Saccharomyces cerevisiae. Gene disruption analysis revealed that P5C-mediated cell death was not due to P5C metabolism. Interestingly, deficiency in mitochondrial respiration suppressed the sensitivity of yeast cells to P5C. In addition, we found that P5C inhibits the mitochondrial respiration and induces a burst of superoxide anions from the mitochondria. We propose that P5C regulates cell death via the inhibition of mitochondrial respiration.
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Akira
A
Nishimura
Ryo
R
Nasuno
Hiroshi
H
Takagi
D000838:Anions; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D015966:Gene Expression Regulation, Fungal; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress; D010101:Oxygen Consumption; D011392:Proline / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013481:Superoxides / Q000737:chemistry; D013997:Time Factors
D000838:Anions; D011758:Pyrroles; D017382:Reactive Oxygen Species; D013481:Superoxides; C015485:delta-1-pyrroline-5-carboxylate; D011392:Proline