Lactate utilization in mitochondria prevents Bax cytotoxicity in yeast Kluyveromyces lactis.
In a search for the physiological conditions able to suppress the disruption of electron transport through the inner mitochondrial membrane induced by Bax, we found that respiratory substrate - lactate completely abolished Bax toxicity in yeast Kluyveromyces lactis. The effect of lactate was dependent on the presence of cytochrome c, as no effect was observed in the cytochrome c null strain. The investigation of lactate effect on markers of Bax toxicity showed that: (i) oxidation of lactate did not affect the decrease in oxygen consumption, but (ii) lactate was able to diminish the generation of reactive oxygen species and simultaneously to suppress Bax-induced cell death. We show that suppression of Bax lethality in K. lactis can be, in addition to anti-apoptotic proteins, achieved also by the utilization of lactate in the mitochondria.
Kost'anová-Poliaková
Daniela
D
Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, 833 91 Bratislava, Slovakia. exondpol@savba.sk
Sabová
L'udmila
L
D000818:Animals; D019069:Cell Respiration / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D007716:Kluyveromyces / Q000166:cytology / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D019344:Lactic Acid; D045304:Cytochromes c