Bioenergetics  ·  Article

Grotthuss mechanism of proton translocation

The Grotthuss mechanism is a proposed way for protons to cross a membrane protein by passing charge along linked water molecules, not by carrying one particle the whole way. Spikes and colleagues invoke it for ATP synthase's inlet half channel5. Morelli and colleagues discuss it for cytochrome c oxidase4. It matters because respiratory proton pumping builds the gradient that drives ATP synthesis6.

Earliest held
1915, Bayliss, W. M.
Most discussed in
An update of the chemiosmotic theory as…, 2019
In the library
40 passages in 13 works
Rewritten
2026-11-01
01

A name with two uses

The name Grotthus is also attached to a rule in photochemistry. Bayliss, in Principles of General Physiology (1915), credited Grotthus (1819) with the first clear statement that light must be absorbed to produce an effect1. Bayliss added that Draper stated it independently at a later date. The rule is frequently called Draper's law1.

02

The proton pumping problem

Wallace (2013) described electrons passing through complexes I, III and IV, with the released energy used to pump protons across the inner membrane. Brzezinski and colleagues (2021) described the same current as driving translocation from matrix to intermembrane space, which maintains a protonmotive force6. Kühlbrandt (2015) noted that how electron transfer is coupled to proton translocation in complex I was still unknown2.

03

Evidence in ATP synthase

Spikes, Montgomery and Walker (2020) reported atomic models of dimeric bovine ATP synthase. They said the models provide evidence for a Grotthus mechanism in the inlet half channel of the membrane domain5. Their keywords list a Grotthus chain5. Nunn, Guy and Bell (2022) cited recent data for an ordered water channel in ATP synthase that could channel protons by this route7. They also said ordered water has been inferred in the proton channel of a V-ATPase7.

04

Doubts and applications

Morelli and colleagues (2019) reviewed work on proton movement in membranes. They noted a paper describing proton diodes, transistors, memories and transducers that use the Grotthuss mechanism3. For complex IV, they named a proton entrance half channel. They said it is hypothesized that another 4 H+, for a total of 8, enter through it4. They judged it unlikely that protons bound to water as particles are equivalent to protons moving as a charge by the Grotthuss mechanism4. Spikes and colleagues, by contrast, took their structures as evidence for the mechanism5.

SourcesEach quotation was checked word for word against the passage it opens.
  1. The law that light must be absorbed in order to produce an effect was first clearly enunciated by Grotthus (1819, p. 101)Bayliss, W. M., 1915 · Principles of General Physiology · open at passage 2355
  2. We still do not know how complex I works, especially how electron transfer is coupled to proton translocation.Kühlbrandt W, 2015 · Structure and function of mitochondrial membrane protein complexes · open at passage 32
  3. presents devices such as proton diodes, transistors, memories and transducers, semiconductor electronic devices that use the Grotthuss mechanismMorelli AM, Ravera S, Calzia D, Panfoli I, 2019 · An update of the chemiosmotic theory as suggested by possible proton currents… · open at passage 23
  4. It seems unlikely that there exists equivalence between protons that exist as particles and link to water molecules and protons that should move as a charge, according to the Grotthuss mechanism.Morelli AM, Ravera S, Calzia D, Panfoli I, 2019 · An update of the chemiosmotic theory as suggested by possible proton currents… · open at passage 31
  5. provide evidence of the operation of a Grotthus mechanism of proton translocation (40) in the inlet half channel of the transmembrane proton pathway through the membrane domain.Spikes TE, Montgomery MG, Walker JE, 2020 · Structure of the dimeric ATP synthase from bovine mitochondria · open at passage 4
  6. The electron current through the respiratory chain drives proton translocation across the membrane, from the inside mitochondrial matrix (negative side, n) to the outside intermembrane space (positive side, p)Brzezinski P, Moe A, Ädelroth P, 2021 · Structure and Mechanism of Respiratory III-IV Supercomplexes in Bioenergetic… · open at passage 1
  7. recent data suggest the presence of an ordered water channel in ATP synthase, which via a Grotthus mechanism, could channel protons.Nunn AVW, Guy GW, Bell JD, 2022 · Bioelectric Fields at the Beginnings of Life · open at passage 25
Linked ideas
The Grotthuss mechanism is offered as one molecular route for protons within the gradient-driven scheme that chemiosmosis describes.
The inlet half channel where Spikes and colleagues report evidence for a Grotthus mechanism lies in the ATP synthase membrane domain.
Oxidative phosphorylationpart of / contains
Proton translocation by the respiratory complexes is the step in oxidative phosphorylation that the mechanism tries to explain.
Kühlbrandt noted that coupling of electron transfer to proton translocation in complex I was unresolved.
Nunn and colleagues inferred ordered water in a V-ATPase proton channel, which links to proton pumping in tissue.
The gradient that proton translocation builds is the membrane potential and pH difference across the inner membrane.
Where it is discussedPassages matching Grotthuss mechanism, Grotthus, proton wire, proton half channel
2019An update of the chemiosmotic theory as suggested by possible proton currents… · Morelli AM, Ravera S, Calzia D, Panfoli…13
2020Structure of the dimeric ATP synthase from bovine mitochondria · Spikes TE, Montgomery MG, Walker JE6
1915Principles of General Physiology · Bayliss, W. M.5
2026Exploring allosteric efflux pump inhibitors and the role of bacterial membrane… · Hada APS, Meena KR, Jitendra, Singh G…4
2015Structure and function of mitochondrial membrane protein complexes · Kühlbrandt W3
2015Pathways and Bioenergetics of Anaerobic Carbon Monoxide Fermentation · Diender M, Stams AJ, Sousa DZ2
2013Bioenergetics in human evolution and disease: implications for the origins of… · Wallace DC1
2026Adenine Nucleotide Translocase: From Nucleotide Carrier to a Modulator of… · Rauch-Kroehnert U, Heger J, Landmesser…1
2021Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions · Protasoni M, Zeviani M1
2022Bioelectric Fields at the Beginnings of Life · Nunn AVW, Guy GW, Bell JD1