Electron Tunneling Rates in Respiratory Complex I Are Tuned for Efficient Energy Conversion

Vries, Simon de; Dörner, Katerina; Strampraad, Marc J. F.; Friedrich, Thorsten

doi:10.1002/anie.201410967

Cited by 62 publications

(68 citation statements)

References 42 publications

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“…Today long-range electron tunnelling is thought to occur in many proteins, and seems to be enhanced by particular molecules, such as the aromatics–which occur more frequently in oxidoreductases, which are key components of respiratory chains [47]. Crucially, it is now thought that electron tunnelling plays an important role in how mitochondria produce energy [48,49] and ensures a tight coupling between electron flow and protonation via a process known as ‘redox tuning’ [50]. In effect, electron tunnelling appears to be a pivotal component of mitochondrial function.…”

Section: The Quantum Anglementioning

confidence: 99%

The quantum mitochondrion and optimal health

Nunn

Guy

Bell

2016

Biochemical Society Transactions

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A sufficiently complex set of molecules, if subject to perturbation, will self-organize and show emergent behaviour. If such a system can take on information it will become subject to natural selection. This could explain how self-replicating molecules evolved into life and how intelligence arose. A pivotal step in this evolutionary process was of course the emergence of the eukaryote and the advent of the mitochondrion, which both enhanced energy production per cell and increased the ability to process, store and utilize information. Recent research suggest that from its inception life embraced quantum effects such as ‘tunnelling’ and ‘coherence’ while competition and stressful conditions provided a constant driver for natural selection. We believe that the biphasic adaptive response to stress described by hormesis–a process that captures information to enable adaptability, is central to this whole process. Critically, hormesis could improve mitochondrial quantum efficiency, improving the ATP/ROS ratio, whereas inflammation, which is tightly associated with the aging process, might do the opposite. This all suggests that to achieve optimal health and healthy aging, one has to sufficiently stress the system to ensure peak mitochondrial function, which itself could reflect selection of optimum efficiency at the quantum level.

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Section: The Quantum Anglementioning

confidence: 99%

The quantum mitochondrion and optimal health

Nunn

Guy

Bell

2016

Biochemical Society Transactions

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“…In the hydrophilic domain, a chain of 8-9 iron-sulfur (FeS) centers connects the NADH/flavin mononucleotide (FMN) site with the Q site (11,25,26), which locates approximately 30 Å above the membrane surface (14). The FeS centers form an electron conduction wire, in which the eT takes place on a microsecond-millisecond timescale between the two ends of the hydrophilic domain (27,28).…”

mentioning

confidence: 99%

Symmetry-related proton transfer pathways in respiratory complex I

Luca

Gámiz‐Hernández

Kaila

2017

Proc. Natl. Acad. Sci. U.S.A.

170

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Complex I functions as the initial electron acceptor in aerobic respiratory chains of most organisms. This gigantic redox-driven enzyme employs the energy from quinone reduction to pump protons across its complete approximately 200-Å membrane domain, thermodynamically driving synthesis of ATP. Despite recently resolved structures from several species, the molecular mechanism by which complex I catalyzes this long-range protoncoupled electron transfer process, however, still remains unclear. We perform here large-scale classical and quantum molecular simulations to study the function of the proton pump in complex I from Thermus thermophilus. The simulations suggest that proton channels are established at symmetry-related locations in four subunits of the membrane domain. The channels open up by formation of quasi one-dimensional water chains that are sensitive to the protonation states of buried residues at structurally conserved broken helix elements. Our combined data provide mechanistic insight into long-range coupling effects and predictions for sitedirected mutagenesis experiments.NADH:ubiquinone oxidoreductase | proton pumping | Grotthuss mechanism | multiscale simulation | bioenergetics C omplex I (NADH:ubiquinone reductase) is the largest enzyme of the respiratory chain, generating a proton motive force (pmf) that is used for synthesis of adenosine triphosphate (ATP) and active transport (1, 2). Complex I catalyzes electron transfer (eT) between nicotine adenine dinucleotide (NADH) and quinone (Q), and couples the energy released to pumping of four protons across the membrane (3-9). The distance between the electron and proton transferring modules extends up to approximately 200 Å. It currently remains unclear, however, how complex I catalyzes this remarkable long-range proton-coupled electron transfer (PCET) process. In addition to its central role in biological energy conversion, elucidating the molecular mechanism of complex

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“…It therefore seems that long-range electron tunnelling may occur in many proteins, in particular in oxidoreductases and key components of respiratory chains [46] and thus may be important in how mitochondria produce energy [46,47], ensuring a tight coupling between electron flow and protonation via redox tuning [48]. It is now also thought that photosynthesis utilises fundamental quantum principles, involving coherence and excitons to transfer energy efficiently [38,39,41] This is especially interesting as lysozyme appears to demonstrate a Fröhlich condensate; Fröhlich suggested that terahertz radiation could be absorbed by proteins leading to them behaving as a series of coupled oscillators generating a macroscopic quantum effect [49].…”

Section: The Emergence Of Quantum Biologymentioning

confidence: 99%

The Hormesis of Thinking: A Deeper Quantum Thermodynamic Perspective?

Nunn¹,

Guy²,

Bell³

2017

Int J Neurorehabilitation Eng

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We are able to read this because of quantum and thermodynamic principles that via an inorganic proton gradient, possibly generated 4.2 billion years ago, gave rise to a system that has an awareness of time and space by using energy to integrate information. Life can be described as a dissipative system driven by an energy gradient that uses information to positively reinforce its self-sustaining structure, which in turn increases its non-linear decisional capacity. Key in the evolution of life has been stress coupled to natural selection, which usually meant an increased demand for energy. As hormesis describes the adaptive response to stress, we propose that hormesis embraces not only the evolution of life, but that of intelligence itself, as natural selection would favour systems that enhances its efficiency. A component of the hormetic response in eukaryotes is the mitochondrion, which itself relies on quantum effects such as tunnelling. This suggests that quantum effects control the stability of individual cells as well as long-lived cellular networks. Hormesis, which can be anti-inflammatory, is therefore key in maintaining the functional stability of complex systems, including the brain. In contrast, a lack of classical hormetic factors, such as physical activity, plant polyphenols, or calorie restriction, will lead to accelerated cognitive decline, which is associated with increased inflammation. However, there may be another previously unidentified factor that could also be considered hormetic, and that is thinking itself. Here we propose that the process of "thinking", and managing complex movement, induces "stress" in the neuronal system and is therefore in itself part of maintaining cognitive health and reserve throughout life. In effect, the right amount of thinking and information processing can beneficially induce adaptation, and this itself could be explainable by quantum thermodynamics.

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Electron Tunneling Rates in Respiratory Complex I Are Tuned for Efficient Energy Conversion

Cited by 62 publications

References 42 publications

The quantum mitochondrion and optimal health

The quantum mitochondrion and optimal health

Symmetry-related proton transfer pathways in respiratory complex I

The Hormesis of Thinking: A Deeper Quantum Thermodynamic Perspective?

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