Editing Electron transport chain (section)

===Mitochondrial redox carriers===<!-- This section is linked from [[Mitochondrion]] -->
Energy associated with the transfer of electrons down the electron transport chain is used to pump protons from the [[mitochondrial matrix]] into the intermembrane space, creating an [[Electrochemical gradient|electrochemical proton gradient]] ([[Oxidative phosphorylation#Chemiosmosis|ΔpH]]) across the inner mitochondrial membrane. This proton gradient is largely but not exclusively responsible for the mitochondrial [[membrane potential]] (ΔΨ{{sub|M}}).<ref name="Zorova">{{cite journal | vauthors = Zorova LD, Popkov VA, Plotnikov EY, Silachev DN, Pevzner IB, Jankauskas SS, Babenko VA, Zorov SD, Balakireva AV, Juhaszova M, Sollott SJ, Zorov DB | display-authors = 6 | title = Mitochondrial membrane potential | journal = Analytical Biochemistry | volume = 552 | pages = 50–59 | date = July 2018 | pmid = 28711444 | pmc = 5792320 | doi = 10.1016/j.ab.2017.07.009 }}</ref> It allows [[ATP synthase]] to use the flow of H<sup>+</sup> through the enzyme back into the matrix to generate ATP from [[adenosine diphosphate]] (ADP) and [[inorganic phosphate]]. Complex I (NADH coenzyme Q reductase; labeled I) accepts electrons from the [[Krebs cycle]] electron carrier [[Nicotinamide adenine dinucleotide|nicotinamide adenine dinucleotide (NADH)]], and passes them to [[coenzyme Q]] ([[ubiquinone]]; labeled Q), which also receives electrons from Complex II ([[succinate dehydrogenase]]; labeled II). Q passes electrons to Complex III ([[cytochrome bc1 complex|cytochrome bc<sub>1</sub> complex]]; labeled III), which passes them to [[cytochrome c|cytochrome ''c'']] (cyt ''c''). Cyt ''c'' passes electrons to Complex IV ([[cytochrome c oxidase|cytochrome ''c'' oxidase]]; labeled IV).{{cn|date=January 2025}}

Four membrane-bound complexes have been identified in mitochondria. Each is an extremely complex [[Transmembrane protein|transmembrane]] structure that is embedded in the inner membrane. Three of them are [[proton pump]]s. The structures are electrically connected by [[lipid-soluble]] electron carriers and water-soluble electron carriers. The overall electron transport chain can be summarized as follows:

 '''NADH, H{{sup|+}}''' → '''''Complex I''''' → '''Q''' → '''''Complex III''''' → '''cytochrome ''c'' '''→ '''''Complex IV''''' → '''H{{sub|2}}O'''
                        ↑
                    '''''Complex II'''''
                        ↑
                    '''Succinate'''

====Complex I====
{{Further|Respiratory complex I}}
In [[Respiratory complex I|Complex I]] (NADH ubiquinone oxidoreductase, Type I NADH dehydrogenase, or mitochondrial complex I; {{EC number|1.6.5.3}}), two electrons are removed from NADH and transferred to a lipid-soluble carrier, ubiquinone (Q). The reduced product, ubiquinol (QH{{sub|2}}), freely diffuses within the membrane, and Complex I translocates four protons (H{{sup|+}}) across the membrane, thus producing a proton gradient. Complex I is one of the main sites at which premature [[electron leakage]] to oxygen occurs, thus being one of the main sites of production of [[superoxide]].<ref name = "Lauren">Lauren, Biochemistry, Johnson/Cole, 2010, pp 598-611</ref>

The pathway of electrons is as follows:

[[NADH]] is oxidized to NAD{{sup|+}}, by reducing [[flavin mononucleotide]] to FMNH{{sub|2}} in one two-electron step. FMNH{{sub|2}} is then oxidized in two one-electron steps, through a [[Ubiquinone#Chemical properties|semiquinone]] intermediate. Each electron thus transfers from the FMNH{{sub|2}} to an [[iron–sulfur cluster|Fe–S cluster]], from the Fe-S cluster to ubiquinone (Q). Transfer of the first electron results in the free-radical ([[Ubiquinone#Chemical properties|semiquinone]]) form of Q, and transfer of the second electron reduces the semiquinone form to the ubiquinol form, QH{{sub|2}}. During this process, four protons are translocated from the mitochondrial matrix to the intermembrane space.<ref name = "Garrett">Garrett & Grisham, Biochemistry, Brooks/Cole, 2010, pp 598-611</ref> As the electrons move through the complex an electron current is produced along the 180 [[Angstrom]] width of the complex within the membrane. This current powers the [[active transport]] of four protons to the intermembrane space per two electrons from NADH.<ref>{{Cite book|title=biochemistry| vauthors = Garrett R, Grisham CM |year=2016|isbn=978-1-305-57720-6| location = Boston | publisher = Cengage |pages=687}}</ref>

====Complex II====
In [[Respiratory complex II|Complex II]] ([[succinate dehydrogenase]] or succinate-CoQ reductase; {{EC number|1.3.5.1}}) additional electrons are delivered into the [[quinone]] pool (Q) originating from succinate and transferred (via [[Flavin adenine dinucleotide|flavin adenine dinucleotide (FAD)]]) to Q. Complex II consists of four protein subunits: succinate dehydrogenase (SDHA); succinate dehydrogenase [ubiquinone] iron–sulfur subunit mitochondrial (SDHB); succinate dehydrogenase complex subunit C (SDHC); and succinate dehydrogenase complex subunit D (SDHD). Other electron donors (e.g., fatty acids and glycerol 3-phosphate) also direct electrons into Q (via FAD). Complex II is a parallel electron transport pathway to Complex I, but unlike Complex I, no protons are transported to the intermembrane space in this pathway. Therefore, the pathway through Complex II contributes less energy to the overall electron transport chain process.{{cn|date=January 2025}}

====Complex III====
In [[Complex III]] ([[cytochrome bc1 complex|cytochrome ''bc<sub>1</sub>'' complex]] or CoQH{{sub|2}}-cytochrome ''c'' reductase; {{EC number|1.10.2.2}}), the [[Q cycle|Q-cycle]] contributes to the proton gradient by an asymmetric absorption/release of protons. Two electrons are removed from QH{{sub|2}} at the Q<sub>O</sub> site and sequentially transferred to two molecules of [[cytochrome c|cytochrome ''c'']], a water-soluble electron carrier located within the intermembrane space. The two other electrons sequentially pass across the protein to the Q<sub>i</sub> site where the quinone part of ubiquinone is reduced to quinol. A proton gradient is formed by one quinol (<chem>2H+2e-</chem>) oxidations at the Q<sub>o</sub> site to form one quinone (<chem>2H+2e-</chem>) at the Q<sub>i</sub> site. (In total, four protons are translocated: two protons reduce quinone to quinol and two protons are released from two ubiquinol molecules.){{cn|date=January 2025}}
: <chem>  QH2 + 2</chem><math> \text{ cytochrome }c</math><chem>(Fe^{III}) + 2 H</chem><math>^+_\text{in}</math><chem> -> Q + 2</chem><math> \text{ cytochrome }c</math><chem>(Fe^{II}) + 4 H</chem><math>^+_\text{out}</math>

When electron transfer is reduced (by a high membrane potential or respiratory inhibitors such as [[antimycin A]]), Complex III may leak electrons to [[molecular oxygen]], resulting in [[superoxide]] formation.

This complex is inhibited by [[dimercaprol]] (British Anti-Lewisite, BAL), [[naphthoquinone]] and antimycin.

====Complex IV====
In [[Complex IV]] ([[cytochrome c oxidase|cytochrome ''c'' oxidase]]; {{EC number|1.9.3.1}}), sometimes called cytochrome AA3, four electrons are removed from four molecules of [[cytochrome c|cytochrome ''c'']] and transferred to molecular oxygen (O{{sub|2}}) and four protons, producing two molecules of water. The complex contains coordinated copper ions and several heme groups. At the same time, eight protons are removed from the mitochondrial matrix (although only four are translocated across the membrane), contributing to the proton gradient. The exact details of proton pumping in Complex IV are still under study.<ref name=":1">{{Cite book|last=Stryer.|title=Biochemistry|publisher=toppan|oclc=785100491}}</ref> [[Cyanide]] is an inhibitor of Complex IV.{{cn|date=January 2025}}