The product of the UTH1 gene, required for Bax-induced cell death in yeast, is involved in the response to rapamycin.
A yeast mutant was isolated that was resistant to Bax-induced cell death. It supports a mutation leading to decreased amounts of the protein Uth1p. A strain in which the UTH1 gene is disrupted also exhibits resistance to Bax expression. The absence of Uth1p does not change the mitochondrial localization of Bax, its insertion in the mitochondrial outer membrane or its cytochrome c-releasing activity. On the other hand, the absence of Uth1p does prevent the appearance of other hallmarks related to Bax expression in yeast, such as oxidation of mitochondrial lipid, production of reactive oxygen species and maintenance of plasma membrane properties after ethanol stress. The absence of Uth1p was also found to induce resistance to rapamycin, a specific inducer of autophagy. This resistance only appears when cells are grown under respiratory conditions, but not under fermentative conditions, suggesting that Uth1p acts in an autophagic pathway involving mitochondria, in accordance with its main localization in the outer mitochondrial membrane. Taken together, these data show that Bax is able to activate a death pathway related to autophagy in yeast, which also exhibits typical hallmarks of apoptosis, revealing a possible dual function of Bax in both types of death. This hypothesis is discussed in the light of observations suggesting a co-regulation of apoptosis and autophagy in mammalian cells.
Camougrand
Nadine
N
UMR5095 CNRS/Université de Bordeaux 2, France.
Grelaud-Coq
Angela
A
Marza
Esther
E
Priault
Muriel
M
Bessoule
Jean-Jacques
JJ
Manon
Stéphen
S
D000935:Antifungal Agents / Q000494:pharmacology; D017209:Apoptosis; D001343:Autophagy; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008565:Membrane Proteins; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D009154:Mutation; D018384:Oxidative Stress; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus / Q000494:pharmacology; D015003:Yeasts / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000935:Antifungal Agents; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D029701:Saccharomyces cerevisiae Proteins; C116477:UTH1 protein, S cerevisiae; D051028:bcl-2-Associated X Protein; D020123:Sirolimus