Marteinn Snæbjörnsson

Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation - Nature Metabolism Snaebjornsson et al. explore a selective vulnerability in cancer elicited by targeting aldolase A, which causes energy imbalance and prevents further metabolic adaptations.

RESEARCH | MT Snaebjornsson, @almutschulze.bsky.social et al. @dkfz.bsky.social

The authors explore a selective vulnerability in #cancer elicited by targeting AldolaseA, which causes #EnergyImbalance and prevents further #metabolic adaptations

https://bit.ly/3Rjn2BX

Fantastic!
Congratulations 🙂

Aldolase A: the broker of glycolysis - Nature Metabolism Aldolase A is one of the glycolytic enzymes that regulate cancer cell proliferation. A new study identifies aldolase A as a critical node that, when inhibited in cancer cells, turns glycolysis into an...

www.nature.com/articles/s42...

Aldolase A: the broker of glycolysis - Nature Metabolism Aldolase A is one of the glycolytic enzymes that regulate cancer cell proliferation. A new study identifies aldolase A as a critical node that, when inhibited in cancer cells, turns glycolysis into an...

This was very much a collaborative effort of the Schulze lab and I would like to thank my current as well as previous coworkers for their key role in bringing this work to light.
Thanks likewise to Alpaslan Tasdogan and coworkers for writing a fantastic News & Views about our work.

This effectively converts glycolysis from an energy producing to an energy consuming pathway in cells that don't really need glycolysis to generate energy. Key to understanding our data was reading the previous work of Bas Teusink lab (PMID: 24436182) in yeast.

Inhibiting Aldolase A leads to imbalanced glycolysis (the investment phase outpaces the payoff phase) where high energy phosphate from ATP is used to synthesize an ever increasing pool of the (high energy) glycolytic intermediate FBP.

Using a combination of metabolomics but also mathematical modeling in collaboration with Prof. Ralf Steuer and Daria Komkova we found that this counterintuitive result is explained by the biphasic and auto-catalytic nature of glycolysis.

We discovered that depleting or knocking out the enzyme Aldolase A in liver cancer lead to cell cycle arrest. Surprisingly, completely blocking glycolysis by knocking out the enzyme GPI upstream of Aldolase in glycolysis was fully tolerated as metabolic reprogramming allowed the cells to adapt.

Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation - Nature Metabolism Snaebjornsson et al. explore a selective vulnerability in cancer elicited by targeting aldolase A, which causes energy imbalance and prevents further metabolic adaptations.

Happy to share our work on the mechanism of glycolysis in cancer now published in the journal Nature Metabolism. This was a large part of my postdoctoral work carried out in the lab of Prof. @almutschulze.bsky.social at the @dkfz.bsky.social and at Uni Wuerzburg.

www.nature.com/articles/s42...