Lane 2022 Abstract Bioblast

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1.1.
Nick Lane
Lane Nick (2022) The alpha and omega of metabolism: why the Krebs cycle brings the earth to life and our own lives to an end. Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001

Link: Bioblast 2022: BEC Inaugural Conference

Lane Nick (2022)

Event: Bioblast 2022

The Krebs cycle is usually perceived as the main source of NADH for oxidative phosphorylation, but it also provides carbon skeletons for the biosynthesis of amino acids, sugars, fatty acids, and by extension nucleotides. This biosynthetic role has become increasingly clear in cancer over the last decade, and Krebs cycle intermediates are now recognized as potent epigenetic signals controlling cellular growth phenotypes via transcription factors such as HIF1α. The biosynthetic basis of the Krebs cycle probably links to the earliest stages of cell evolution, where the longer reverse cycle is central to the structure of biochemistry. Recent experimental work shows that protometabolism probably arose from the reaction of H2 and CO2 in alkaline hydrothermal systems, in which steep proton gradients across Fe(Ni)S barriers drove the synthesis of Krebs-cycle intermediates and onwards flux into core protometabolism. I will show that the topology of pores and protocells (and even the Earth) has been preserved in the structure of prokaryotic cells, where reversible flux through the Krebs cycle is intimately associated with the proton-motive force and membrane potential. After the emergence of oxygenic photosynthesis and the accumulation of oxygen, Krebs-cycle flux became delicately poised as a mutual symbiosis between tissues in early animals, enabling them to adapt to persistent hypoxia and euxinia. At the Cambrian explosion, accelerated metabolic rates in the presence of oxygen forced evolutionary choices between repair and reproduction, hence ageing, with the consequence being diminished oxidative phosphorylation with age. I will show why it is not possible for some cells to alter their Krebs-cycle flux, notably pancreatic beta cells and neurons, which calibrate their membrane potential according to glucose availability. This link between Krebs-cycle flux and membrane potential might point to the emergence of elementary consciousness in single-celled organisms, including bacteria, in which fluctuations in membrane potential and the electrical fields generated amount to real-time integrated feedback on the homeostatic state of cells in relation to the outside world – the electrochemical basis of a ‘feeling’.


O2k-Network Lab: UK London Lane N


Affiliations

Department of Genetics, Evolution and Environment, University College London - nick.lane@ucl.ac.uk

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