title: Oxidation of the yeast mitochondrial thioredoxin promotes cell death.
abstract: OBJECTIVE
  Yeast, like other eukaryotes, contains a complete mitochondrial thioredoxin system comprising a thioredoxin (Trx3) and a thioredoxin reductase (Trr2). Mitochondria are a main source of reactive oxygen species (ROS) in eukaryotic organisms, and this study investigates the role of Trx3 in regulating cell death during oxidative stress conditions.
  
  
  RESULTS
  We have previously shown that the redox state of mitochondrial Trx3 is buffered by the glutathione redox couple such that oxidized mitochondrial Trx3 only accumulates in mutants simultaneously lacking Trr2 and a glutathione reductase (Glr1). We show here that the redox state of mitochondrial Trx3 is important for yeast growth and its oxidation in a glr1 trr2 mutant induces programmed cell death. Apoptosis is dependent on the Yca1 metacaspase, since loss of YCA1 abrogates cell death induced by oxidized Trx3. Our data also indicate a role for a mitochondrial 1-cysteine (Cys) peroxiredoxin (Prx1) in the oxidation of Trx3, since Trx3 does not become oxidized in glr1 trr2 mutants or in a wild-type strain exposed to hydrogen peroxide in the absence of PRX1.
  
  
  METHODS
  This study provides evidence that the redox state of a mitochondrial thioredoxin regulates yeast apoptosis in response to oxidative stress conditions. Moreover, the results identify a signaling pathway, where the thioredoxin system functions in both antioxidant defense and in controlling cell death.
  
  
  CONCLUSIONS
  Mitochondrial Prx1 functions as a redox signaling molecule that oxidizes Trx3 and promotes apoptosis. This would mean that under conditions where Prx1 cannot detoxify mitochondrial ROS, it induces cell death to remove the affected cells.
authors: Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors: Darren
authors: D
authors: Greetham
authors: Paraskevi
authors: P
authors: Kritsiligkou
authors: Rachel H
authors: RH
authors: Watkins
authors: Zorana
authors: Z
authors: Carter
authors: Jill
authors: J
authors: Parkin
authors: Chris M
authors: CM
authors: Grant
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D020134:Catalytic Domain; D017124:Conserved Sequence; D055786:Gene Knockout Techniques; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010544:Peroxidases / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D054482:Thioredoxin Reductase 2 / Q000235:genetics; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C508746:GLR1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C541128:Trx3 protein, S cerevisiae; D013879:Thioredoxins; D006861:Hydrogen Peroxide; C410041:PRX1 protein, S cerevisiae; D010544:Peroxidases; D054482:Thioredoxin Reductase 2; D020169:Caspases; C456272:MCA1 protein, S cerevisiae; D005978:Glutathione