Lactate utilization in mitochondria prevents Bax cytotoxicity in yeast Kluyveromyces lactis

FEBS Lett. 2005 Sep 26;579(23):5152-6. doi: 10.1016/j.febslet.2005.08.026.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Respiration / physiology
  • Cytochromes c / metabolism
  • Kluyveromyces / cytology
  • Kluyveromyces / metabolism*
  • Lactic Acid / metabolism*
  • Mice
  • Mitochondria / metabolism*
  • Oxidation-Reduction
  • Oxygen Consumption
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / toxicity*
  • Reactive Oxygen Species / metabolism
  • bcl-2-Associated X Protein

Substances

  • Bax protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Lactic Acid
  • Cytochromes c