Production of reactive oxygen species and loss of viability in yeast mitochondrial mutants: protective effect of Bcl-xL.
The capacity of yeast cells to produce reactive oxygen species (ROS), both as a response to manipulation of mitochondrial functions and to growth conditions, was estimated and compared with the viability of the cells. The chronological ageing of yeast cells (growth to late-stationary phase) was accompanied by increased ROS accumulation and a significantly higher loss of viability in the mutants with impaired mitochondrial functions than in the parental strain. Under these conditions, the ectopic expression of mammalian Bcl-x(L), which is an anti-apoptotic protein, allowed cells to survive longer in stationary phase. The protective effect of Bcl-x(L) was more prominent in respiratory-competent cells that contained defects in mitochondrial ADP/ATP translocation, suggesting a model for Bcl-x(L) regulation of chronological ageing at the mitochondria. Yeast can also be triggered into apoptosis-like cell death, at conditions leading to the depletion of the intramitochondrial ATP pool, as a consequence of the parallel inhibition of mitochondrial respiration and ADP/ATP translocation. If respiratory-deficient (rho(0)) cells were used, no correlation between the numbers of ROS-producing cells and the viability loss in the population was observed, indicating that ROS production may be an accompanying event. The protective effect of Bcl-x(L) against death of these cells suggests a mitochondrial mechanism which is different from the antioxidant activity of Bcl-x(L).
Department of Biochemistry, Faculty of Sciences, Comenius University, Mlynska Dolina CH-1, 842 15 Bratislava, Slovakia.
Alzbeta
A
Trancíková
Petronela
P
Weisová
Ingrid
I
Kissová
Igor
I
Zeman
Jordan
J
Kolarov
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D001865:Bongkrekic Acid / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000502:physiology; D015151:Immunoblotting; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D016296:Mutagenesis; D010101:Oxygen Consumption / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D051020:bcl-X Protein
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051020:bcl-X Protein; D001865:Bongkrekic Acid; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D003576:Electron Transport Complex IV