Editing Electron transport chain (section)

===Coupling with oxidative phosphorylation===
[[File:ATP-Synthase.svg|thumb|240px|Depiction of [[ATP synthase]], the site of oxidative phosphorylation to generate ATP.]]
According to the [[chemiosmosis|chemiosmotic coupling hypothesis]], proposed by [[Nobel Prize in Chemistry]] winner [[Peter D. Mitchell]], the electron transport chain and [[oxidative phosphorylation]] are coupled by a proton gradient across the inner mitochondrial membrane. The efflux of protons from the mitochondrial matrix creates an [[electrochemical gradient]] (proton gradient). This gradient is used by the F{{sub|O}}F{{sub|1}} [[ATP synthase]] complex to make ATP via oxidative phosphorylation. ATP synthase is sometimes described as ''Complex V'' of the electron transport chain.<ref>{{cite journal | vauthors = Jonckheere AI, Smeitink JA, Rodenburg RJ | title = Mitochondrial ATP synthase: architecture, function and pathology | journal = Journal of Inherited Metabolic Disease | volume = 35 | issue = 2 | pages = 211–25 | date = March 2012 | pmid = 21874297 | pmc = 3278611 | doi = 10.1007/s10545-011-9382-9 }}</ref> The F{{sub|O}} component of [[ATP synthase]] acts as an [[ion channel]] that provides for a proton flux back into the mitochondrial matrix. It is composed of a, b and c subunits. Protons in the inter-membrane space of mitochondria first enter the ATP synthase complex through an ''a'' subunit channel. Then protons move to the c subunits.<ref name=":0">{{Cite book|title=Biochemistry| vauthors = Garrett RH, Grisham CM |publisher=Cengage learning|year=2012|isbn=978-1-133-10629-6|edition=5th|pages=664}}</ref> The number of c subunits determines how many protons are required to make the F{{sub|O}} turn one full revolution. For example, in humans, there are 8 c subunits, thus 8 protons are required.<ref>{{cite journal | vauthors = Fillingame RH, Angevine CM, Dmitriev OY | title = Mechanics of coupling proton movements to c-ring rotation in ATP synthase | journal = FEBS Letters | volume = 555 | issue = 1 | pages = 29–34 | date = November 2003 | pmid = 14630314 | doi = 10.1016/S0014-5793(03)01101-3 | s2cid = 38896804 | doi-access = free }}</ref> After ''c'' subunits, protons finally enter the matrix through an ''a'' subunit channel that opens into the mitochondrial matrix.<ref name=":0" /> This reflux releases [[Gibb's free energy|free energy]] produced during the generation of the oxidized forms of the electron carriers (NAD{{sup|+}} and Q) with energy provided by O{{sub|2}}. The free energy is used to drive ATP synthesis, catalyzed by the F{{sub|1}} component of the complex.<ref>{{Cite journal|last1=Berg|first1=Jeremy M.|last2=Tymoczko|first2=John L.|last3=Stryer|first3=Lubert | name-list-style = vanc |date=2002-01-01|title=A Proton Gradient Powers the Synthesis of ATP|url=https://www.ncbi.nlm.nih.gov/books/NBK22388/|language=en}}</ref><br>Coupling with oxidative phosphorylation is a key step for ATP production. However, in specific cases, uncoupling the two processes may be biologically useful. The uncoupling protein, [[thermogenin]]—present in the inner mitochondrial membrane of [[brown adipose tissue]]—provides for an alternative flow of protons back to the inner mitochondrial matrix. Thyroxine is also a natural uncoupler. This alternative flow results in [[thermogenesis]] rather than ATP production.<ref>{{cite journal | vauthors = Cannon B, Nedergaard J | title = Brown adipose tissue: function and physiological significance | journal = Physiological Reviews | volume = 84 | issue = 1 | pages = 277–359 | date = January 2004 | pmid = 14715917 | doi = 10.1152/physrev.00015.2003 | url = http://physrev.physiology.org/content/84/1/277 | url-access = subscription }}</ref>