TY - UNPB
T1 - Oxygen dependent mitochondrial formate production and the reverse Pasteur effect
AU - Meiser, Johannes
AU - Vazquez, Alexei
N1 - Authors retain copyright and choose from several distribution/reuse options under which to make the article available (CC BY, CC BY-NC, CC BY-ND, CC BY-NC-ND, CC0, or no reuse).
PY - 2020/4/10
Y1 - 2020/4/10
N2 - The Pasteur effect dictates that oxygen induces respiration and represses fermentation. However, we have shown that oxygen stimulates mitochondrial formate production and excess formate production induces glycolysis in mammalian cells. Our observations suggest the hypothesis that increased respiration induces an increase, rather than a decrease, of fermentation, the reverse Pasteur effect. Using a mathematical model we show that, in the absence of mitochondrial formate production, we should always observe the Pasteur effect, a reduction in fermentation with increasing respiration. However, in cells with active mitochondrial formate production, the rate of fermentation first increases with increasing the rate of respiration, indicating a metabolic sweet spot at moderate oxygen availability that is within the range of tissue oxygen tensions. We provide experimental evidence for the manifestation of the reverse Pasteur effect at such oxygen tension.
### Competing Interest Statement
The authors have declared no competing interest.
AB - The Pasteur effect dictates that oxygen induces respiration and represses fermentation. However, we have shown that oxygen stimulates mitochondrial formate production and excess formate production induces glycolysis in mammalian cells. Our observations suggest the hypothesis that increased respiration induces an increase, rather than a decrease, of fermentation, the reverse Pasteur effect. Using a mathematical model we show that, in the absence of mitochondrial formate production, we should always observe the Pasteur effect, a reduction in fermentation with increasing respiration. However, in cells with active mitochondrial formate production, the rate of fermentation first increases with increasing the rate of respiration, indicating a metabolic sweet spot at moderate oxygen availability that is within the range of tissue oxygen tensions. We provide experimental evidence for the manifestation of the reverse Pasteur effect at such oxygen tension.
### Competing Interest Statement
The authors have declared no competing interest.
KW - biochemistry
U2 - 10.1101/2020.04.10.035675
DO - 10.1101/2020.04.10.035675
M3 - Preprint
BT - Oxygen dependent mitochondrial formate production and the reverse Pasteur effect
ER -