A study of evolutionary cell biology demonstrates how energy production can be tuned to assure rapid growth without respiration.

The Randall Centre for Cell and Molecular Biophysics and the Crick Institute use an evolutionary cell biology approach to identify the critical points at which respiration feeds into central carbon metabolism in two related fission yeasts, one of which acquires energy through respiration and the other of which does not.

For our comprehension of life, from evolution to development to disease, it is essential to establish the rules of carbon metabolism, which generates biomass and energy. Glycolysis is an old metabolic pathway that doesn’t require oxygen. One atom of glucose is utilized to create two particles of ATP — the “energy money” of the cell — and two atoms of pyruvate, a moderate atom that can be processed further in the breath. The most effective method for producing ATP and regenerating the electron carrier NAD+, which is necessary for growth, is respiration (which, in mammals, can produce up to 36 ATPs per glucose).

The majority of eukaryotes, including animals, fungi, and plants, live in oxygen-rich environments and breathe. However, even when oxygen is available, rapidly growing human cancer cells and single-cell organisms like yeast frequently choose glycolysis over respiration. The metabolic rewiring required to deal with a lack of respiration is poorly understood.

The new paper, which was published in Current Biology, discusses the possible tradeoffs of choosing between glycolysis and respiration and how to optimize both ATP production and NAD+ regeneration for rapid growth without respiration.

The researchers are persuaded that gaining an understanding of metabolism’s plasticity may, in the long run, make it easier to explain organismal ecology and the development of higher-level cellular characteristics like cell size and growth rate. The standards uncovered in this study can be possibly summed up as the reconstruction of energy digestion in human maturing and sickness and the direction of new ways toward working on microbial execution in biotechnological applications.

More information: Snezhana Oliferenko, Optimisation of energy production and central carbon metabolism in a non-respiring eukaryote, Current Biology (2023). DOI: 10.1016/ … 0960-9822(23)00528-6

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