Reverse electron transfer: Difference between revisions

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Reverse electron flow

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+#REDIRECT [[Reverse electron flow]]
-'''Reverse electron transfer''' ('''RET''') is the process that can occur in respiring [[mitochondria]], when a small fraction of electrons from [[reduced]] [[ubiquinol]] is driven upstream by the [[membrane potential]] towards to [[mitochondrial complex I]]. This result in [[reduction]] of [[oxidized]] pyridine nucleotide ([[NAD]]<sup>+</sup> or [[NADP]]<sup>+</sup>). This is a reversal of [[exergonic]] reaction of forward [[electron transfer]] in the mitochondrial complex I when electrons travel from [[NADH]] to [[ubiquinone]].
-==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]]. [[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 [[Britton Chance|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)<sup>+</sup>).<ref>{{cite journal |last1=Chance |first1=Britton |author-link1=Britton Chance |last2=Hollunger |first2=Gunnar |title=Energy-Linked Reduction of Mitochondrial Pyridine Nucleotide |journal=Nature |date=March 1960 |volume=185 |issue=4714 |pages=666–672 |doi=10.1038/185666a0|pmid=13809106 |bibcode=1960Natur.185..666C |s2cid=4267386 }}</ref>. When succinate is oxidized by intact mitochondria, complex I can [[catalyze]] ''reverse'' electron transfer when a electrons from [[ubiquinol]] (QH<sub>2</sub>, 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 electon transfer in the 60s' 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<ref>{{cite journal |last1=Niatsetskaya |first1=Z. V. |last2=Sosunov |first2=S. A. |last3=Matsiukevich |first3=D. |last4=Utkina-Sosunova |first4=I. V. |last5=Ratner |first5=V. I. |last6=Starkov |first6=A. A. |last7=Ten |first7=V. S. |title=The Oxygen Free Radicals Originating from Mitochondrial Complex I Contribute to Oxidative Brain Injury Following Hypoxia-Ischemia in Neonatal Mice |journal=Journal of Neuroscience |date=2012-02-29 |volume=32 |issue=9 |pages=3235–3244 |doi=10.1523/JNEUROSCI.6303-11.2012|pmid=22378894 |pmc=3296485 }}</ref> and heart.<ref>{{cite journal |last1=Chouchani |first1=Edward T. |last2=Pell |first2=Victoria R. |last3=Gaude |first3=Edoardo |last4=Aksentijević |first4=Dunja |last5=Sundier |first5=Stephanie Y. |last6=Robb |first6=Ellen L. |last7=Logan |first7=Angela |last8=Nadtochiy |first8=Sergiy M. |last9=Ord |first9=Emily N. J. |last10=Smith |first10=Anthony C. |last11=Eyassu |first11=Filmon |last12=Shirley |first12=Rachel |last13=Hu |first13=Chou-Hui |last14=Dare |first14=Anna J. |last15=James |first15=Andrew M. |last16=Rogatti |first16=Sebastian |last17=Hartley |first17=Richard C. |last18=Eaton |first18=Simon |last19=Costa |first19=Ana S. H. |last20=Brookes |first20=Paul S. |last21=Davidson |first21=Sean M. |last22=Duchen |first22=Michael R. |last23=Saeb-Parsy |first23=Kourosh |last24=Shattock |first24=Michael J. |last25=Robinson |first25=Alan J. |last26=Work |first26=Lorraine M. |last27=Frezza |first27=Christian |last28=Krieg |first28=Thomas |last29=Murphy |first29=Michael P. |title=Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS |journal=Nature |date=2014-11-20 |volume=515 |issue=7527 |pages=431–435 |doi=10.1038/nature13909|pmid=25383517 |pmc=4255242 |bibcode=2014Natur.515..431C }}</ref> During ischemia substantial amount of succinate is generated in cerebral<ref>{{cite journal |last1=Sahni |first1=PV |last2=Zhang |first2=J |last3=Sosunov |first3=S |last4=Galkin |first4=A |last5=Niatsetskaya |first5=Z |last6=Starkov |first6=A |last7=Brookes |first7=PS |last8=Ten |first8=VS |title=Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice. |journal=Pediatric research |date=2018 |volume=83 |issue=2 |pages=491-497 |doi=10.1038/pr.2017.277 |pmid=29211056}}</ref> or cardiac tissue<ref>{{cite journal |last1=Pisarenko |first1=O |last2=Studneva |first2=I |last3=Khlopkov |first3=V |title=Metabolism of the tricarboxylic acid cycle intermediates and related amino acids in ischemic guinea pig heart. |journal=Biomedica biochimica acta |date=1987 |volume=46 |issue=8-9 |pages=568-571 |pmid=2893608}}</ref> 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-electon reduction of oxygen takes place. <ref>{{cite journal |last1=Andreyev |first1=A. Yu. |last2=Kushnareva |first2=Yu. E. |last3=Starkov |first3=A. A. |title=Mitochondrial metabolism of reactive oxygen species |journal=Biochemistry (Moscow) |date=2005 |volume=70 |issue=2 |pages=200–214 |doi=10.1007/s10541-005-0102-7|pmid=15807660 |s2cid=17871230 }}</ref><ref>{{cite journal |last1=Quinlan |first1=Casey L. |last2=Perevoshchikova |first2=Irina V. |last3=Hey-Mogensen |first3=Martin |last4=Orr |first4=Adam L. |last5=Brand |first5=Martin D. |title=Sites of reactive oxygen species generation by mitochondria oxidizing different substrates |journal=Redox Biology |date=2013 |volume=1 |issue=1 |pages=304–312 |doi=10.1016/j.redox.2013.04.005|pmid=24024165 |pmc=3757699 }}</ref><ref>{{cite journal |last1=Stepanova |first1=Anna |last2=Kahl |first2=Anja |last3=Konrad |first3=Csaba |last4=Ten |first4=Vadim |last5=Starkov |first5=Anatoly S |last6=Galkin |first6=Alexander |title=Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia reperfusion injury |journal=Journal of Cerebral Blood Flow & Metabolism |date=December 2017 |volume=37 |issue=12 |pages=3649–3658 |doi=10.1177/0271678X17730242|pmid=28914132 |pmc=5718331 }}</ref>
-== References ==
-{{reflist}}