Metabolic Trade-offs in Yeast are Caused by F1F0-ATP synthase
Journal article, 2016

Intermediary metabolism provides living cells with free energy and precursor metabolites required for synthesizing proteins, lipids, RNA and other cellular constituents, and it is highly conserved among living species. Only a fraction of cellular protein can, however, be allocated to enzymes of intermediary metabolism and consequently metabolic trade-offs may take place. One such trade-off, aerobic fermentation, occurs in both yeast (the Crabtree effect) and cancer cells (the Warburg effect) and has been a scientific challenge for decades. Here we show, using flux balance analysis combined with in vitro measured enzyme specific activities, that fermentation is more catalytically efficient than respiration, i.e. it produces more ATP per protein mass. And that the switch to fermentation at high growth rates therefore is a consequence of a high ATP production rate, provided by a limited pool of enzymes. The catalytic efficiency is also higher for cells grown on glucose compared to galactose and ethanol, which may explain the observed differences in their growth rates. The enzyme F1F0-ATP synthase (Complex V) was found to have flux control over respiration in the model, and since it is evolutionary conserved, we expect the trade-off to occur in organisms from all kingdoms of life.

Author

Avlant Nilsson

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Scientific Reports

2045-2322 (ISSN)

Vol. 6 22264

Subject Categories

Industrial Biotechnology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.1038/srep22264

More information

Created

10/7/2017