Editing Oxidative phosphorylation (section)

== Reactive oxygen species ==
{{further|Oxidative stress|Antioxidant}}
Molecular oxygen is a good terminal [[electron acceptor]] because it is a strong oxidizing agent. The reduction of oxygen does involve potentially harmful intermediates.<ref name=Davies>{{cite journal | vauthors = Davies KJ | title = Oxidative stress: the paradox of aerobic life | journal = Biochemical Society Symposium | volume = 61 | pages = 1–31 | year = 1995 | pmid = 8660387 | doi = 10.1042/bss0610001 }}</ref> Although the transfer of four electrons and four protons reduces oxygen to water, which is harmless, transfer of one or two electrons produces [[superoxide]] or [[peroxide]] anions, which are dangerously reactive.

{{NumBlk|:|<chem>O2 ->[\ce{e^-}] \underset{Superoxide}{O2^{\underline{\bullet}}} ->[\ce{e^-}] \underset{Peroxide}{O2^{2-}}</chem>|{{EquationRef|7}}}}

These [[reactive oxygen species]] and their reaction products, such as the [[hydroxyl]] radical, are very harmful to cells, as they oxidize proteins and cause [[mutation]]s in [[DNA]]. This cellular damage may contribute to [[disease]] and is proposed as one cause of [[free-radical theory of aging|aging]].<ref>{{cite journal | vauthors = Rattan SI | title = Theories of biological aging: genes, proteins, and free radicals | journal = Free Radical Research | volume = 40 | issue = 12 | pages = 1230–1238 | date = December 2006 | pmid = 17090411 | doi = 10.1080/10715760600911303 | url = http://www.link-age.eu/Freeradicalresearch-Rattan.pdf | url-status = dead | access-date = 2017-10-27 | s2cid = 11125090 | citeseerx = 10.1.1.476.9259 | archive-url = https://web.archive.org/web/20140614080412/http://www.link-age.eu/Freeradicalresearch-Rattan.pdf | archive-date = 2014-06-14 }}</ref><ref>{{cite journal | vauthors = Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J | title = Free radicals and antioxidants in normal physiological functions and human disease | journal = The International Journal of Biochemistry & Cell Biology | volume = 39 | issue = 1 | pages = 44–84 | year = 2007 | pmid = 16978905 | doi = 10.1016/j.biocel.2006.07.001 }}</ref>

The cytochrome c oxidase complex is highly efficient at reducing oxygen to water, and it releases very few partly reduced intermediates; however small amounts of superoxide anion and peroxide are produced by the electron transport chain.<ref name=Raha>{{cite journal | vauthors = Raha S, Robinson BH | title = Mitochondria, oxygen free radicals, disease and ageing | journal = Trends in Biochemical Sciences | volume = 25 | issue = 10 | pages = 502–508 | date = October 2000 | pmid = 11050436 | doi = 10.1016/S0968-0004(00)01674-1 }}</ref> Particularly important is the reduction of [[coenzyme Q]] in complex III, as a highly reactive ubisemiquinone free radical is formed as an intermediate in the Q cycle. This unstable species can lead to electron "leakage" when electrons transfer directly to oxygen, forming superoxide.<ref>{{cite journal | vauthors = Finkel T, Holbrook NJ | title = Oxidants, oxidative stress and the biology of ageing | journal = Nature | volume = 408 | issue = 6809 | pages = 239–247 | date = November 2000 | pmid = 11089981 | doi = 10.1038/35041687 | s2cid = 2502238 | bibcode = 2000Natur.408..239F }}</ref> As the production of reactive oxygen species by these proton-pumping complexes is greatest at high membrane potentials, it has been proposed that mitochondria regulate their activity to maintain the membrane potential within a narrow range that balances ATP production against oxidant generation.<ref>{{cite journal | vauthors = Kadenbach B, Ramzan R, Wen L, Vogt S | title = New extension of the Mitchell Theory for oxidative phosphorylation in mitochondria of living organisms | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1800 | issue = 3 | pages = 205–212 | date = March 2010 | pmid = 19409964 | doi = 10.1016/j.bbagen.2009.04.019 }}</ref> For instance, oxidants can activate [[uncoupling protein]]s that reduce membrane potential.<ref>{{cite journal | vauthors = Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD | title = Superoxide activates mitochondrial uncoupling proteins | journal = Nature | volume = 415 | issue = 6867 | pages = 96–99 | date = January 2002 | pmid = 11780125 | doi = 10.1038/415096a | s2cid = 4349744 | bibcode = 2002Natur.415...96E }}</ref>

To counteract these reactive oxygen species, cells contain numerous [[antioxidant]] systems, including antioxidant [[vitamin]]s such as [[vitamin C]] and [[vitamin E]], and antioxidant enzymes such as [[superoxide dismutase]], [[catalase]], and [[peroxidases]],<ref name=Davies/> which detoxify the reactive species, limiting damage to the cell.