View source for Respiratory complex I

== Function ==

[[Image:NAD+toNADH.png|thumb|class=skin-invert-image|274x274px|NAD<sup>+</sup> to NADH.]]
[[Image:FMN to FMNH2.svg|thumb|class=skin-invert-image|274x274px|FMN to FMNH<sub>2</sub>.]]
[[Image:QtoQH2.png|thumb|class=skin-invert-image|276x276px|CoQ to CoQH<sub>2</sub>.]]

Complex I is the first enzyme of the [[Electron transport chain#Mitochondrial electron transport chains|mitochondrial electron transport chain]]. There are three energy-transducing enzymes in the electron transport chain - NADH:ubiquinone oxidoreductase (complex I), [[Coenzyme Q – cytochrome c reductase]] (complex III), and [[cytochrome c oxidase]] (complex IV).<ref name="Berg">{{cite book | vauthors = Berg J, Tymoczko J, Stryer L | title = Biochemistry | edition = 6th | publisher = WH Freeman & Company | location = New York | year = 2006  | pages = 509–513 }}</ref> Complex I is the largest and most complicated enzyme of the electron transport chain.<ref name = "pmid16756485">{{cite journal | vauthors = Brandt U | title = Energy converting NADH:quinone oxidoreductase (complex I) | journal = Annual Review of Biochemistry | volume = 75 | pages = 69–92 | year = 2006 | pmid = 16756485 | doi = 10.1146/annurev.biochem.75.103004.142539 }}</ref>

The reaction catalyzed by complex I is:

:NADH + H<sup>+</sup> + CoQ + 4H<sup>+</sup><sub>in</sub>→ NAD<sup>+</sup> + CoQH<sub>2</sub> + 4H<sup>+</sup><sub>out</sub>

In this process, the complex translocates four [[proton pump|protons]] across the inner membrane per molecule of oxidized [[NADH]],<ref>{{cite journal | vauthors = Wikström M | title = Two protons are pumped from the mitochondrial matrix per electron transferred between NADH and ubiquinone | journal = FEBS Letters | volume = 169 | issue = 2 | pages = 300–4 | date = April 1984 | pmid = 6325245 | doi = 10.1016/0014-5793(84)80338-5 | bibcode = 1984FEBSL.169..300W | doi-access = free }}</ref><ref name="pmid17094937">{{cite journal | vauthors = Galkin A, Dröse S, Brandt U | title = The proton pumping stoichiometry of purified mitochondrial complex I reconstituted into proteoliposomes | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1757 | issue = 12 | pages = 1575–81 | date = December 2006 | pmid = 17094937 | doi = 10.1016/j.bbabio.2006.10.001 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Galkin AS, Grivennikova VG, Vinogradov AD | title = →H+/2e- stoichiometry in NADH-quinone reductase reactions catalyzed by bovine heart submitochondrial particles | journal = FEBS Letters | volume = 451 | issue = 2 | pages = 157–61 | date = May 1999 | pmid = 10371157 | doi = 10.1016/s0014-5793(99)00575-x | s2cid = 2337382 | doi-access = free }}</ref> helping to build the [[electrochemical potential]] difference used to produce [[Adenosine triphosphate|ATP]]. ''[[Escherichia coli]]'' complex I (NADH dehydrogenase) is capable of proton translocation in the same direction to the established [[Water potential|Δψ]], showing that in the tested conditions, the coupling ion is H<sup>+</sup>.<ref name="Batista 286–292">{{cite journal | vauthors = Batista AP, Pereira MM | title = Sodium influence on energy transduction by complexes I from Escherichia coli and Paracoccus denitrificans | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1807 | issue = 3 | pages = 286–92 | date = March 2011 | pmid = 21172303 | doi = 10.1016/j.bbabio.2010.12.008 | doi-access = free }}</ref> Na<sup>+</sup> transport in the opposite direction was observed, and although Na<sup>+</sup> was not necessary for the catalytic or proton transport activities, its presence increased the latter. H<sup>+</sup> was translocated by the ''[[Paracoccus denitrificans]]'' complex I, but in this case, H<sup>+</sup> transport was not influenced by Na<sup>+</sup>, and Na<sup>+</sup> transport was not observed. Possibly, the ''E. coli'' complex I has two energy coupling sites (one Na<sup>+</sup> independent and the other Na<sup>+</sup>dependent), as observed for the ''[[Rhodothermus marinus]]'' complex I, whereas the coupling mechanism of the ''P. denitrificans'' enzyme is completely Na<sup>+</sup> independent. It is also possible that another transporter catalyzes the uptake of Na<sup>+</sup>. Complex I energy transduction by proton pumping may not be exclusive to the ''R. marinus'' enzyme. The Na<sup>+</sup>/H<sup>+</sup> antiport activity seems not to be a general property of complex I.<ref name="Batista 286–292"/> However, the existence of Na<sup>+</sup>-translocating activity of the complex I is still in question.

The reaction can be reversed – referred to as aerobic succinate-supported NAD<sup>+</sup> reduction by ubiquinol – in the presence of a high membrane potential, but the exact catalytic mechanism remains unknown. Driving force of this reaction is a potential across the membrane which can be maintained either by ATP-hydrolysis or by complexes III and IV during succinate oxidation.<ref name="pmid17760425">{{cite journal | vauthors = Grivennikova VG, Kotlyar AB, Karliner JS, Cecchini G, Vinogradov AD | title = Redox-dependent change of nucleotide affinity to the active site of the mammalian complex I | journal = Biochemistry | volume = 46 | issue = 38 | pages = 10971–8 | date = September 2007 | pmid = 17760425 | pmc = 2258335 | doi = 10.1021/bi7009822 }}</ref>

Complex I may have a role in triggering [[apoptosis]].<ref name="pmid20371875">{{cite journal | vauthors = Chomova M, Racay P | title = Mitochondrial complex I in the network of known and unknown facts | journal = General Physiology and Biophysics | volume = 29 | issue = 1 | pages = 3–11 | date = March 2010 | pmid = 20371875 | doi = 10.4149/gpb_2010_01_3 | doi-access = free }}</ref> In fact, there has been shown to be a correlation between mitochondrial activities and [[programmed cell death]] (PCD) during somatic embryo development.<ref name="pmid 19834734">{{cite journal | vauthors = Petrussa E, Bertolini A, Casolo V, Krajnáková J, Macrì F, Vianello A | title = Mitochondrial bioenergetics linked to the manifestation of programmed cell death during somatic embryogenesis of Abies alba | journal = Planta | volume = 231 | issue = 1 | pages = 93–107 | date = December 2009 | pmid = 19834734 | doi = 10.1007/s00425-009-1028-x | bibcode = 2009Plant.231...93P | s2cid = 25828432 }}</ref>

Complex I is not homologous to '''Na<sup>+</sup>-translocating NADH Dehydrogenase (NDH) Family''' ([http://tcdb.org/search/result.php?tc=3.D.1 TC# 3.D.1]), a member of the [[Mrp superfamily|Na<sup>+</sup> transporting Mrp superfamily]].

As a result of a two NADH molecule being oxidized to NAD+, three molecules of ATP can be produced by Complex V ([[ATP synthase]]) downstream in the respiratory chain.