Publication highlights

Establishing the rules of carbon metabolism, which produces biomass and energy, is critical for our understanding of life, from evolution to development to disease. Glycolysis is an ancient metabolic pathway which doesn't need oxygen - one molecule of glucose is used to produce two molecules of ATP, the “energy currency” of the cell, and two molecules of pyruvate, an intermediate molecule which can be metabolised further in respiration. Respiration is the most efficient way of generating ATP (overall producing up to 36 ATPs/glucose in mammals) and regenerating the electron carrier NAD+, which is required for growth. Most eukaryotes - like animals, fungi or plants -  live in environments with lots of oxygen, and respire. Yet, rapidly growing human cancer cells and single cell organisms, such as yeasts, often choose glycolysis over respiration, even when oxygen is available. We know little about the metabolic rewiring required to cope with the lack of respiration.

Here the researchers use an evolutionary cell biology approach in two related fission yeasts, one which acquires energy by respiration and one which doesn't, to find the critical points at which respiration feeds into central carbon metabolism. They show how both ATP production and NAD+ regeneration can be optimized to ensure rapid growth and discuss possible trade-offs of choosing between respiration and glycolysis.