Membrane bioenergetics are as universally conserved across life as the genetic code. Ion electrochemical gradients across membranes, notably proton gradients, are responsible for driving ATP synthesis via chemiosmotic coupling, but also CO2 fixation through proton- motive membrane-integral Fe(Ni)S proteins such as the energy-converting hydrogenase (Ech). Modern membrane bioenergetics couple electron transfer through multiple redox centres to proton extrusion across the membrane, generating a proton-motive force that powers work.

The idea that electrons tunnel between redox centres goes back to Britton Chance in the 1960s, who showed that electron transfer is independent of temperature 1. More recent work shows that the distance between redox centres is under selection, with shorter distances facilitating tunnelling even against redox potential 2. How such complex machinery first arose has long been mysterious, but the question is greatly simplified by the hypothesis that life began in alkaline hydrothermal vents, pioneered over 30 years by Mike Russell 3.

The interconnected inorganic micropores in hydrothermal systems frustrate mixing, sustaining steep proton gradients across barriers containing Fe(Ni)S minerals, with a topology and magnitude equivalent to cells 4. Microfluidic work shows that vectorial electron transfer from H2 to CO2 in these systems is pH dependent, with the inorganic barrier maintaining phase separation in a similar way to the cell membrane 5. Differences in pH modulate the redox potentials of H2, CO2 and FeS clusters according to the Nernst equation (~-59 mV per pH unit), whereby H2 is more reducing in alkaline conditions and CO2 more easily reduced in acidic conditions, with electron transfer between the two phases requiring electron tunnelling across Fe(Ni)S nanocrystals 6.

Our own work uses Ech as a guide to the origin of membrane bioenergetics in alkaline hydrothermal systems 6. Ech contains four Fe(Ni)S clusters, two of which are pH sensitive with their redox potential varying by around -50 mV per pH unit 7. We propose that proton binding increases the redox potential of the Fe(Ni)S ‘wire’ through the resonance effects of tunnelling, allowing Ech to oxidise H2. Transient closure of the proton pore allows proton dissociation, lowering the redox potential of Ech by >200 mV, facilitating the apparently endergonic reduction of ferredoxin 6.

Electron tunnelling therefore operates as a redox switch, in which the redox potential of the whole Fe(Ni)S ‘wire’ is sensitive to local protonation through transient exposure to the extracellular phase via the membrane pore. In broader terms, electron tunnelling enables communication between separate phases with distinct redox potentials, coupling flux to CO2 reduction and potentially powering growth in geologically structured systems.

We have shown that protocells can form from mixtures of simple amphiphiles under these conditions 8 and will line Fe(Ni)S barriers 9, focusing proton gradients onto the cell membranes themselves. FeS clusters can form spontaneously through chelation by amino acids such as cysteine.

If these clusters associate with the membranes of protocells in a geologically structured system, then electron tunnelling in the presence of steep proton gradients should drive CO2 reduction, powering protocell growth at the origin of life.

References

1. De Vault D, Chance B. Studies of photosynthesis using a pulsed laser. I. Temperature dependence of cytochrome oxidation rate in Chromatium. Evidence for tunneling. Biophys J 6: 825-847 (1966).
2. Page CC, et al. Natural engineering principles of electron tunnelling in biological oxidation-reduction. Nature 402: 47-52 (1999).
3. Cartwright JHE, Russell MJ. The origin of life: the submarine alkaline vent theory at 30. Interface focus 9: 20190104 (2019).
4. Nitschke W, Russell MJ. Hydrothermal focusing of chemical and chemiosmotic energy, supported by delivery of catalytic Fe, Ni, Mo/W, Co, S and Se, forced life to emerge. J Mol Evol 69: 481-496 (2009).
5. Hudson R, e al. CO2 reduction driven by a pH gradient. Proc Natl Acad Sci USA 117: 22873-79 (2020).
6. Vasiliadou R, et al. Possible mechanisms of CO2 reduction by H2 via prebiotic vectorial electrochemistry. Interface focus 9: 20190073 (2019).
7. Kurkin S, et al. The membrane-bound [NiFe]-hydrogenase (Ech) from Methanosarcina barkeri: unusual properties of the iron-sulphur clusters. Eur J Biochem 269: 6101-11 (2002).
8. Jordan SF, et al. Promotion of protocell self-assembly from mixed amphiphiles at the origin of life. Nature Ecol Evol 3: 1705-14 (2019).
9. Jordan SF, Nee E, Lane N. Isoprenoids enhance the stability of fatty acid membranes at the emergence of life potentially leading to an early lipid divide. Interface focus 9: 20190067 (2019).

Procedings of 2nd Guy Foundation Symposium on Quantum Biology and Bioenergetics, Autumn 2020. The Guy Foundation ‘2020 Autumn Series’ with the theme ‘Does biology utilise environmental noise to amplify quantum effects?’