Chemiosmosis is the movement of
ions across a
semipermeable membrane
Semipermeable membrane is a type of synthetic or biologic, polymeric membrane that allows certain molecules or ions to pass through it by osmosis. The rate of passage depends on the pressure, concentration, and temperature of the molecules o ...
bound structure, down their
electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts:
* The chemical gradient, or difference in Concentration, solute concentration across ...
. An important example is the formation of
adenosine triphosphate (ATP) by the movement of
hydrogen
Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...
ions (H
+) across a
membrane
A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...
during
cellular respiration
Cellular respiration is the process of oxidizing biological fuels using an inorganic electron acceptor, such as oxygen, to drive production of adenosine triphosphate (ATP), which stores chemical energy in a biologically accessible form. Cell ...
or
photosynthesis
Photosynthesis ( ) is a system of biological processes by which photosynthetic organisms, such as most plants, algae, and cyanobacteria, convert light energy, typically from sunlight, into the chemical energy necessary to fuel their metabo ...
.

Hydrogen ions, or
proton
A proton is a stable subatomic particle, symbol , Hydron (chemistry), H+, or 1H+ with a positive electric charge of +1 ''e'' (elementary charge). Its mass is slightly less than the mass of a neutron and approximately times the mass of an e ...
s, will
diffuse from a region of high proton concentration to a region of lower proton concentration, and an
electrochemical concentration gradient of protons across a membrane can be harnessed to make ATP. This process is related to
osmosis
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively permeable membrane, selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of ...
, the movement of
water
Water is an inorganic compound with the chemical formula . It is a transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance. It is the main constituent of Earth's hydrosphere and the fluids of all known liv ...
across a selective membrane, which is why it is called "chemiosmosis".
ATP synthase is the
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that makes ATP by chemiosmosis. It allows protons to pass through the membrane and uses the
free energy difference to convert
phosphorylate adenosine diphosphate
Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is essential to the flow of energy in living cells. ADP consists of three important structural components: a sugar backbon ...
(ADP) into ATP. The ATP synthase contains two parts: CF0 (present in thylakoid membrane) and CF1 (protrudes on the outer surface of thylakoid membrane). The breakdown of the proton gradient leads to conformational change in CF1—providing enough energy in the process to convert ADP to ATP. The generation of ATP by chemiosmosis occurs in
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
and
chloroplast
A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...
s, as well as in most
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
and
archaea
Archaea ( ) is a Domain (biology), domain of organisms. Traditionally, Archaea only included its Prokaryote, prokaryotic members, but this has since been found to be paraphyletic, as eukaryotes are known to have evolved from archaea. Even thou ...
. For instance, in
chloroplasts during photosynthesis, an electron transport chain pumps H
+ ions (protons) in the
stroma (fluid) through the thylakoid membrane to the thylakoid spaces. The stored energy is used to
photophosphorylate ADP, making ATP, as protons move through ATP synthase.
The chemiosmotic hypothesis
Peter D. Mitchell proposed the chemiosmotic hypothesis in 1961. In brief, the hypothesis was that most
adenosine triphosphate
Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...
(ATP) synthesis in
respiring cells comes from the
electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts:
* The chemical gradient, or difference in Concentration, solute concentration across ...
across the inner membranes of
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
by using the
energy
Energy () is the physical quantity, quantitative physical property, property that is transferred to a physical body, body or to a physical system, recognizable in the performance of Work (thermodynamics), work and in the form of heat and l ...
of
NADH and
FADH2 formed during the oxidative breakdown of energy-rich
molecule
A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
s such as
glucose
Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
.
Molecules such as glucose are
metabolized to produce
acetyl CoA as a fairly energy-rich intermediate. The
oxidation
Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
of
acetyl coenzyme A (acetyl-CoA) in the
mitochondrial matrix is coupled to the
reduction of a carrier molecule such as
nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphat ...
(NAD) and
flavin adenine dinucleotide (FAD).
The carriers pass
electron
The electron (, or in nuclear reactions) is a subatomic particle with a negative one elementary charge, elementary electric charge. It is a fundamental particle that comprises the ordinary matter that makes up the universe, along with up qua ...
s to the
electron transport chain
An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
(ETC) in the
inner mitochondrial membrane
The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space.
Structure
The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...
, which in turn pass them to other proteins in the ETC. The energy at every redox transfer step is used to pump
proton
A proton is a stable subatomic particle, symbol , Hydron (chemistry), H+, or 1H+ with a positive electric charge of +1 ''e'' (elementary charge). Its mass is slightly less than the mass of a neutron and approximately times the mass of an e ...
s from the
matrix
Matrix (: matrices or matrixes) or MATRIX may refer to:
Science and mathematics
* Matrix (mathematics), a rectangular array of numbers, symbols or expressions
* Matrix (logic), part of a formula in prenex normal form
* Matrix (biology), the m ...
into the intermembrane space, storing energy in the form of a transmembrane
electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts:
* The chemical gradient, or difference in Concentration, solute concentration across ...
. The protons move back across the inner membrane through the enzyme
ATP synthase. The flow of protons back into the matrix of the mitochondrion via
ATP synthase provides enough energy for ADP to combine with inorganic
phosphate
Phosphates are the naturally occurring form of the element phosphorus.
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...
to form ATP.
This was a radical proposal at the time, and was not well accepted. The prevailing view was that the energy of electron transfer was stored as a stable high potential intermediate, a chemically more conservative concept. The problem with the older paradigm is that no high energy intermediate was ever found, and the evidence for proton pumping by the complexes of the
electron transfer chain grew too great to be ignored. Eventually the weight of evidence began to favor the chemiosmotic hypothesis, and in 1978
Peter D. Mitchell was awarded the
Nobel Prize in Chemistry.
Chemiosmotic coupling is important for ATP production in
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
,
chloroplast
A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...
s
and many
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
and
archaea
Archaea ( ) is a Domain (biology), domain of organisms. Traditionally, Archaea only included its Prokaryote, prokaryotic members, but this has since been found to be paraphyletic, as eukaryotes are known to have evolved from archaea. Even thou ...
.
Proton-motive force

The movement of ions across the membrane depends on a combination of two factors:
#
Diffusion
Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
force caused by a concentration gradient - all particles tend to diffuse from higher concentration to lower.
#
Electrostatic force caused by
electrical potential gradient -
cations like protons H
+ tend to diffuse down the electrical potential, from the positive (P) side of the membrane to the negative (N) side.
Anions diffuse spontaneously in the opposite direction.
These two gradients taken together can be expressed as an
electrochemical gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts:
* The chemical gradient, or difference in Concentration, solute concentration across ...
.
Lipid bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes form a continuous barrier around all cell (biology), cells. The cell membranes of almost all organisms and many viruses a ...
s of
biological membranes, however, are barriers for ions. This is why energy can be stored as a combination of these two gradients across the membrane. Only special membrane proteins like
ion channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...
s can sometimes allow ions to move across the membrane (see also:
Membrane transport). In the chemiosmotic hypothesis a transmembrane
ATP synthase is central to convert energy of spontaneous flow of protons through them into chemical energy of ATP bonds.
Hence researchers created the term proton-motive force (PMF), derived from the electrochemical gradient mentioned earlier. It can be described as the measure of the potential energy stored (
chemiosmotic potential) as a combination of proton and voltage (electrical potential) gradients across a membrane. The electrical gradient is a consequence of the charge separation across the membrane (when the protons H
+ move without a
counterion, such as
chloride
The term chloride refers to a compound or molecule that contains either a chlorine anion (), which is a negatively charged chlorine atom, or a non-charged chlorine atom covalently bonded to the rest of the molecule by a single bond (). The pr ...
Cl
−).
In most cases the proton-motive force is generated by an electron transport chain which acts as a proton pump, using the
Gibbs free energy
In thermodynamics, the Gibbs free energy (or Gibbs energy as the recommended name; symbol is a thermodynamic potential that can be used to calculate the maximum amount of Work (thermodynamics), work, other than Work (thermodynamics)#Pressure–v ...
of
redox
Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is t ...
reactions to pump protons (hydrogen ions) out across the membrane, separating the charge across the membrane. In mitochondria, energy released by the electron transport chain is used to move protons from the mitochondrial matrix (N side) to the intermembrane space (P side). Moving the protons out of the mitochondrion creates a lower concentration of positively charged protons inside it, resulting in excess negative charge on the inside of the membrane. The electrical potential gradient is about -170 mV , negative inside (N). These gradients - charge difference and the proton concentration difference both create a combined electrochemical gradient across the membrane, often expressed as the proton-motive force (PMF). In mitochondria, the PMF is almost entirely made up of the electrical component but in chloroplasts the PMF is made up mostly of the pH gradient because the charge of protons H
+ is neutralized by the movement of Cl
− and other anions. In either case, the PMF needs to be greater than about 460 mV (45 kJ/mol) for the ATP synthase to be able to make ATP.
Equations
The proton-motive force is derived from the
Gibbs free energy
In thermodynamics, the Gibbs free energy (or Gibbs energy as the recommended name; symbol is a thermodynamic potential that can be used to calculate the maximum amount of Work (thermodynamics), work, other than Work (thermodynamics)#Pressure–v ...
. Let N denote the inside of a cell, and P denote the outside. Then
:
where
*
is the Gibbs free energy change per unit amount of
cation
An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s transferred from P to N;
*
is the
charge number of the
cation
An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
;
*
is the electric potential of N relative to P;
*
and
are the cation concentrations at P and N, respectively;
*
is the
Faraday constant
In physical chemistry, the Faraday constant (symbol , sometimes stylized as ℱ) is a physical constant defined as the quotient of the total electric charge () by the amount () of elementary charge carriers in any given sample of matter: it ...
;
*
is the
gas constant; and
*
is the
temperature
Temperature is a physical quantity that quantitatively expresses the attribute of hotness or coldness. Temperature is measurement, measured with a thermometer. It reflects the average kinetic energy of the vibrating and colliding atoms making ...
.
The molar Gibbs free energy change
is frequently interpreted as a molar electrochemical ion potential
.
For an electrochemical proton gradient
and as a consequence:
:

where
:
.
Mitchell defined the proton-motive force (PMF) as
:
.
For example,
implies
. At
this equation takes the form:
.
Note that for spontaneous proton import from the P side (relatively more positive and acidic) to the N side (relatively more negative and alkaline),
is negative (similar to
) whereas PMF is positive (similar to redox cell potential
).
It is worth noting that, as with any transmembrane transport process, the PMF is directional. The sign of the transmembrane electric potential difference
is chosen to represent the change in potential energy per unit charge flowing into the cell as above. Furthermore, due to redox-driven proton pumping by coupling sites, the proton gradient is always inside-alkaline. For both of these reasons, protons flow in spontaneously, from the P side to the N side; the available free energy is used to synthesize ATP (see below). For this reason, PMF is defined for proton import, which is spontaneous. PMF for proton export, i.e., proton pumping as catalyzed by the coupling sites, is simply the negative of PMF(import).
The spontaneity of proton import (from the P to the N side) is universal in all bioenergetic membranes. This fact was not recognized before the 1990s, because the chloroplast thylakoid lumen was interpreted as an interior phase, but in fact it is topologically equivalent to the exterior of the chloroplast. Azzone et al. stressed that the inside phase (N side of the membrane) is the bacterial cytoplasm, mitochondrial matrix, or chloroplast stroma; the outside (P) side is the bacterial periplasmic space, mitochondrial intermembrane space, or chloroplast lumen. Furthermore, 3D tomography of the mitochondrial inner membrane shows its extensive invaginations to be stacked, similar to thylakoid disks; hence the mitochondrial intermembrane space is topologically quite similar to the chloroplast lumen.:
The energy expressed here as Gibbs free energy, electrochemical proton gradient, or proton-motive force (PMF), is a combination of two gradients across the membrane:
# the concentration gradient (via
) and
# electric potential gradient
.
When a system reaches equilibrium,
; nevertheless, the concentrations on either side of the membrane need not be equal. Spontaneous movement across the potential membrane is determined by both concentration and electric potential gradients.
The molar Gibbs free energy
of ATP synthesis
:
is also called phosphorylation potential. The equilibrium concentration ratio