Reverse electron flow (also known as reverse electron transport) is a mechanism in

microbial metabolism Microbial metabolism is the means by which a microbe obtains the energy and nutrients (e.g. carbon) it needs to live and reproduce. Microbes use many different types of metabolic strategies and species can often be differentiated from each other ...

Chemolithotroph Lithotrophs are a diverse group of organisms using an inorganic substrate (usually of mineral origin) to obtain reducing equivalents for use in biosynthesis (e.g., carbon dioxide fixation) or energy conservation (i.e., ATP production) via aerob ...

s using an

electron donor In chemistry, an electron donor is a chemical entity that transfers electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process. An obsolete definition equated an electron dono ...

with a higher

redox potential Redox potential (also known as oxidation / reduction potential, ''ORP'', ''pe'', ''E_'', or E_) is a measure of the tendency of a chemical species to acquire electrons from or lose electrons to an electrode and thereby be reduced or oxidised respe ...

than NAD(P)⁺/NAD(P)H, such as nitrite or sulfur compounds, must use energy to reduce NAD(P)⁺. This energy is supplied by consuming

proton motive force Chemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient. An important example is the formation of adenosine triphosphate (ATP) by the movement of hydrogen ions (H+) across a membra ...

to drive electrons in a reverse direction through an

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 ...

and is thus the reverse process as forward electron transport. In some cases, the energy consumed in reverse electron transport is five times greater than energy gained from the forward process.

Autotroph An autotroph is an organism that can convert Abiotic component, abiotic sources of energy into energy stored in organic compounds, which can be used by Heterotroph, other organisms. Autotrophs produce complex organic compounds (such as carbohy ...

s can use this process to supply reducing power for inorganic

carbon fixation Biological carbon fixation, or сarbon assimilation, is the Biological process, process by which living organisms convert Total inorganic carbon, inorganic carbon (particularly carbon dioxide, ) to Organic compound, organic compounds. These o ...

. Reverse electron transfer (RET) is the process that can occur in respiring

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 ...

, when a small fraction of electrons from reduced

ubiquinol A ubiquinol is an electron-rich (reduced) form of coenzyme Q (ubiquinone). The term most often refers to ubiquinol-10, with a 10-unit tail most commonly found in humans. The natural ubiquinol form of coenzyme Q is 2,3-dimethoxy-5-methyl-6-poly p ...

is driven upstream by the

membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. It equals the interior potential minus the exterior potential. This is th ...

towards mitochondrial complex I. This results in reduction of

oxidized 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 ...

pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...

nucleotide (

NAD NAD or Nad may refer to: Geography * Nad, County Cork, a village in Ireland * North American Datum, a series of geographic coordinate systems * North Atlantic Drift, an Atlantic Ocean current * Hobli, a subdivision of a taluka in southern Ind ...

⁺ or

NADP Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require N ...

⁺). This is a reversal of the

exergonic An exergonic process is one which there is a positive flow of energy from the system to the surroundings. This is in contrast with an endergonic process. Constant pressure, constant temperature reactions are exergonic if and only if the Gibbs ...

reaction of forward

electron transfer Electron transfer (ET) occurs when an electron relocates from an atom, ion, or molecule, to another such chemical entity. ET describes the mechanism by which electrons are transferred in redox reactions. Electrochemical processes are ET reactio ...

in the mitochondrial complex I when electrons travel from

NADH Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...

ubiquinone Coenzyme Q10 (CoQ10 ), also known as ubiquinone, is a naturally occurring Cofactor (biochemistry), biochemical cofactor (coenzyme) and an antioxidant produced by the human body. It can also be obtained from dietary sources, such as meat, fish, ...

Mechanism

The term "Reverse electron transfer" is used in regard to the reversibility of the reaction performed by complex I of the mitochondrial or bacterial

respiratory 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 this ...

Complex I Respiratory complex I, (also known as NADH:ubiquinone oxidoreductase, Type I NADH dehydrogenase and mitochondrial complex I) is the first large protein complex of the respiratory chains of many organisms from bacteria to humans. It catalyzes th ...

is responsible for 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 ...

generated in

catabolism Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipid ...

when in the ''forward'' reaction electrons from the nucleotide (NADH) are transferred to membrane

and energy is saved in the form of

proton-motive force Chemiosmosis is the movement of ions across a semipermeable membrane bound structure, down their electrochemical gradient. An important example is the formation of adenosine triphosphate (ATP) by the movement of hydrogen ions (H+) across a membra ...

. The reversibility of the electron transfer reactions at complex I was first discovered when Chance and Hollunger have shown that the addition of

succinate Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into Fuma ...

to mitochondria in State 4 leads to an uncoupler-sensitive reduction of the intramitochondrial

nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

(NAD(P)⁺). When succinate is oxidized by intact mitochondria, complex I can

catalyze Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

''reverse'' electron transfer when electrons from

(QH₂, formed during oxidation of succinate) is driven by the proton-motive force to complex I flavin toward the nucleotide-binding site. Since the discovery of the reverse electron transfer in the 1960s it was regarded as in vitro phenomenon, until the role of RET in the development of

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

reperfusion injury Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue ('' re-'' + ''perfusion'') after a period of ischemia or lack of oxygen (anoxia or hy ...

has been recognized in the brain and heart. During ischemia substantial amount of succinate is generated in cerebral or cardiac tissue and upon reperfusion it can be oxidized by mitochondria initiating reverse electron transfer reaction. Reverse electron transfer supports the highest rate of mitochondrial Reactive Oxygen Species ( ROS) production, and complex I

flavin mononucleotide Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as the prosthetic group of various oxidoreductases, including NADH dehydrogenase, as ...

(FMN) has been identified as the site where one-electron reduction of oxygen takes place.

References

{{reflist Metabolism