Reverse electron flow (also known as reverse electron transport) is a mechanism in
microbial metabolism.
Chemolithotrophs using an
electron donor with a higher
redox potential 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 to drive electrons in a reverse direction through an
electron transport chain 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.[1]Autotrophs can use this process to supply reducing power for inorganic
carbon fixation.
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.
Complex I is responsible for the
oxidation of
NADH generated in
catabolism when in the forward reaction electrons from the nucleotide (NADH) are transferred to membrane
ubiquinone and energy is saved in the form of
proton-motive force. The reversibility of the electron transfer reactions at complex I was first discovered when
Chance and Hollunger have shown that the addition of
succinate to mitochondria in State 4 leads to an
uncoupler-sensitive reduction of the intramitochondrial nucleotides (NAD(P)+).[2] When succinate is oxidized by intact mitochondria, complex I can
catalyzereverse electron transfer when electrons from
ubiquinol (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/
reperfusion injury has been recognized in the brain[3] and heart.[4] During ischemia substantial amount of succinate is generated in cerebral[5] or cardiac tissue[6] 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 (FMN) has been identified as the site where one-electron reduction of oxygen takes place.[7][8][9]
^Chouchani, Edward T.; Pell, Victoria R.; Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y.; Robb, Ellen L.; Logan, Angela; Nadtochiy, Sergiy M.; Ord, Emily N. J.; Smith, Anthony C.; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Hartley, Richard C.; Eaton, Simon; Costa, Ana S. H.; Brookes, Paul S.; Davidson, Sean M.; Duchen, Michael R.; Saeb-Parsy, Kourosh; Shattock, Michael J.; Robinson, Alan J.; Work, Lorraine M.; Frezza, Christian; Krieg, Thomas; Murphy, Michael P. (2014-11-20).
"Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS". Nature. 515 (7527): 431–435.
Bibcode:
2014Natur.515..431C.
doi:
10.1038/nature13909.
PMC4255242.
PMID25383517.
^Pisarenko, O; Studneva, I; Khlopkov, V (1987). "Metabolism of the tricarboxylic acid cycle intermediates and related amino acids in ischemic guinea pig heart". Biomedica Biochimica Acta. 46 (8–9): 568–571.
PMID2893608.
^Andreyev, A. Yu.; Kushnareva, Yu. E.; Starkov, A. A. (2005). "Mitochondrial metabolism of reactive oxygen species". Biochemistry (Moscow). 70 (2): 200–214.
doi:
10.1007/s10541-005-0102-7.
PMID15807660.
S2CID17871230.