Editing Oxidative phosphorylation (section)

==== Reoxygenation of intolerant animals ====
When oxygen re-enters the system, animals are faced with a different set of problems. Since ATP was used up during the anoxic period, it leads to a lack of [[ADP-ribose diphosphatase|ADP]] within the system.<ref name="Bundgaard_2019">{{cite journal | vauthors = Bundgaard A, James AM, Gruszczyk AV, Martin J, Murphy MP, Fago A | title = Metabolic adaptations during extreme anoxia in the turtle heart and their implications for ischemia-reperfusion injury | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 2850 | date = February 2019 | pmid = 30808950 | pmc = 6391391 | doi = 10.1038/s41598-019-39836-5 | bibcode = 2019NatSR...9.2850B }}</ref> This is due to ADP's natural degradation into AMP, resulting in ADP being drained from the system. With no ADP in the system, Complex V is unable to start, meaning the protons will not flow through it to enter the matrix.<ref name="Bundgaard_2019" /> Due to Complex V's reversal during anoxia, the proton gradient has become hyperpolarized (where the proton gradient is highly positively charged). Another factor in this problem is that [[Succinic acid|succinate]] built up during anoxia, so when oxygen is reintroduced, succinate donates electrons to [[Succinate dehydrogenase|Complex II]].<ref name="Bundgaard_2024">{{cite journal | vauthors = Bundgaard A, Borowiec BG, Lau GY | title = Are reactive oxygen species always bad? Lessons from hypoxic ectotherms | journal = The Journal of Experimental Biology | volume = 227 | issue = 6 | pages = jeb246549 | date = March 2024 | pmid = 38533673 | doi = 10.1242/jeb.246549 | bibcode = 2024JExpB.227B6549B }}</ref><ref name="Chouchani_2014">{{cite journal | vauthors = Chouchani ET, Pell VR, Gaude E, Aksentijević D, Sundier SY, Robb EL, Logan A, Nadtochiy SM, Ord EN, Smith AC, Eyassu F, Shirley R, Hu CH, Dare AJ, James AM, Rogatti S, Hartley RC, Eaton S, Costa AS, Brookes PS, Davidson SM, Duchen MR, Saeb-Parsy K, Shattock MJ, Robinson AJ, Work LM, Frezza C, Krieg T, Murphy MP | title = Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS | journal = Nature | volume = 515 | issue = 7527 | pages = 431–435 | date = November 2014 | pmid = 25383517 | pmc = 4255242 | doi = 10.1038/nature13909 | bibcode = 2014Natur.515..431C }}</ref> The hyperpolarized gradient and succinate buildup leads to [[Reverse electron flow|reverse electron transport]], causing [[oxidative stress]],<ref name="Murphy_2009">{{cite journal | vauthors = Murphy MP | title = How mitochondria produce reactive oxygen species | journal = The Biochemical Journal | volume = 417 | issue = 1 | pages = 1–13 | date = January 2009 | pmid = 19061483 | pmc = 2605959 | doi = 10.1042/BJ20081386 }}</ref> which can lead to cellular damage and diseases.<ref name="Bolisetty_2013">{{cite journal | vauthors = Bolisetty S, Jaimes EA | title = Mitochondria and reactive oxygen species: physiology and pathophysiology | journal = International Journal of Molecular Sciences | volume = 14 | issue = 3 | pages = 6306–6344 | date = March 2013 | pmid = 23528859 | pmc = 3634422 | doi = 10.3390/ijms14036306 | doi-access = free }}</ref>