Editing Reactive oxygen species (section)

==Sources of ROS production==
[[File:Major cellular sources of Reactive Oxygen Species in living cells.jpg|thumb|Major cellular sources of ROS in living non-[[photosynthesis|photosynthetic]] cells. From a review by Novo and Parola, 2008.<ref name="pmid19014652">{{Cite journal |vauthors=Novo E, Parola M |date=October 2008 |title=Redox mechanisms in hepatic chronic wound healing and fibrogenesis |journal=Fibrogenesis & Tissue Repair |volume=1 |issue=1 |pages=5 |doi=10.1186/1755-1536-1-5 |pmc=2584013 |pmid=19014652 |doi-access=free}}</ref><ref name="Nachiappan">{{Cite journal |vauthors=Muthukumar K, Nachiappan V |date=December 2010 |title=Cadmium-induced oxidative stress in Saccharomyces cerevisiae |url=http://nopr.niscair.res.in/handle/123456789/10863 |journal=Indian Journal of Biochemistry & Biophysics |volume=47 |issue=6 |pages=383–387 |pmid=21355423}}</ref>]]

===Endogenous sources===
ROS are produced during the processes of respiration and photosynthesis in organelles such as [[mitochondria]], [[peroxisomes]] and [[chloroplasts]].<ref name="auto" /><ref>{{Cite journal |vauthors=Dietz KJ |date=January 2016 |title=Thiol-Based Peroxidases and Ascorbate Peroxidases: Why Plants Rely on Multiple Peroxidase Systems in the Photosynthesizing Chloroplast? |journal=Molecules and Cells |volume=39 |issue=1 |pages=20–25 |doi=10.14348/molcells.2016.2324 |pmc=4749869 |pmid=26810073}}</ref><ref name="Muller2000">{{Cite journal |vauthors=Muller F |date=October 2000 |title=The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging |journal=Journal of the American Aging Association |volume=23 |issue=4 |pages=227–253 |doi=10.1007/s11357-000-0022-9 |pmc=3455268 |pmid=23604868}}</ref><ref name="pmid11139407">{{Cite journal |vauthors=Han D, Williams E, Cadenas E |date=January 2001 |title=Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space |journal=The Biochemical Journal |volume=353 |issue=Pt 2 |pages=411–416 |doi=10.1042/0264-6021:3530411 |pmc=1221585 |pmid=11139407}}</ref> During the respiration process the mitochondria convert energy for the cell into a usable form, [[adenosine triphosphate]] (ATP). The process of ATP production in the mitochondria, called [[oxidative phosphorylation]], involves the transport of [[protons]] (hydrogen ions) across the inner mitochondrial membrane by means of the [[electron transport chain]]. In the electron transport chain, electrons are passed through a series of [[protein]]s via oxidation-reduction reactions, with each acceptor [[protein]] along the chain having a greater reduction potential than the previous. The last destination for an electron along this chain is an oxygen molecule. In normal conditions, the oxygen is reduced to produce water; however, in about 0.1–2% of electrons passing through the chain (this number derives from studies in isolated mitochondria, though the exact rate in live organisms is yet to be fully agreed upon), oxygen is instead prematurely and incompletely reduced to give the [[superoxide radical]] (<sup>•</sup>{{chem|O|2|−}}), most well documented for [[Complex I]] and [[Complex III]].<ref name="pmid23442817">{{Cite journal |vauthors=Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF |date=February 2013 |title=Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers |journal=Journal of Hematology & Oncology |volume=6 |issue=19 |pages=19 |doi=10.1186/1756-8722-6-19 |pmc=3599349 |pmid=23442817 |doi-access=free}}</ref>

Another source of ROS production in animal cells is the electron transfer reactions catalyzed by the mitochondrial [[P450]] systems in [[steroidogenic]] tissues.<ref name="1993-Hanukoglu">{{Cite journal |vauthors=Hanukoglu I, Rapoport R, Weiner L, Sklan D |date=September 1993 |title=Electron leakage from the mitochondrial NADPH-adrenodoxin reductase-adrenodoxin-P450scc (cholesterol side chain cleavage) system |url=https://zenodo.org/record/890721 |journal=Archives of Biochemistry and Biophysics |volume=305 |issue=2 |pages=489–498 |doi=10.1006/abbi.1993.1452 |pmid=8396893}}</ref>
These P450 systems are dependent on the transfer of electrons from [[NADPH]] to P450. During this process, some electrons "leak" and react with O<sub>2</sub> producing superoxide. To cope with this natural source of ROS, the steroidogenic tissues, ovary and testis, have a large concentration of [[antioxidant]]s such as [[vitamin C]] (ascorbate) and [[β-carotene]] and anti-oxidant enzymes.<ref name="2006-Hanukoglu">{{Cite journal |vauthors=Hanukoglu I |year=2006 |title=Antioxidant protective mechanisms against reactive oxygen species (ROS) generated by mitochondrial P450 systems in steroidogenic cells |url=https://zenodo.org/record/890701 |journal=Drug Metabolism Reviews |volume=38 |issue=1–2 |pages=171–196 |doi=10.1080/03602530600570040 |pmid=16684656 |s2cid=10766948}}</ref>

If too much damage is present in mitochondria, a cell undergoes [[apoptosis]] or programmed cell death.<ref>{{Cite journal |vauthors=Curtin JF, Donovan M, Cotter TG |date=July 2002 |title=Regulation and measurement of oxidative stress in apoptosis |url=https://arrow.dit.ie/cgi/viewcontent.cgi?article=1039&context=scschbioart |journal=Journal of Immunological Methods |volume=265 |issue=1–2 |pages=49–72 |doi=10.1016/s0022-1759(02)00070-4 |pmid=12072178}}</ref><ref>{{Cite book |title=Molecular Biology of the Cell |vauthors=Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P |date=2014 |publisher=Garland Science |isbn=978-0-8153-4432-2 |edition=6th |location=New York |pages=1025}}</ref>

In addition, ROS are produced in immune cell signaling via the [[NADPH oxidase|NOX]] pathway. Phagocytic cells such as [[neutrophils]], [[eosinophils]], and mononuclear [[phagocyte]]s produce ROS when stimulated.<ref name="Functions of ROS in Macrophages and">{{Cite journal |vauthors=Herb M, Schramm M |date=February 2021 |title=Functions of ROS in Macrophages and Antimicrobial Immunity |journal=Antioxidants |volume=10 |issue=2 |page=313 |doi=10.3390/antiox10020313 |pmc=7923022 |pmid=33669824 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Chen X, Song M, Zhang B, Zhang Y |date=July 28, 2016 |title=Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment |journal=Oxidative Medicine and Cellular Longevity |volume=2016 |pages=1580967 |doi=10.1155/2016/1580967 |pmc=4980531 |pmid=27547291 |doi-access=free}}</ref>

In [[chloroplasts]], the [[carboxylation]] and oxygenation reactions catalyzed by [[rubisco]] ensure that the functioning of the electron transport chain (ETC) occurs in an environment rich in O<sub>2</sub>. The leakage of electrons in the ETC will inevitably produce ROS within the chloroplasts.<ref name="auto" />
ETC in photosystem I (PSI) was once believed to be the only source of ROS in chloroplasts. The flow of electrons from the excited reaction centers is directed to the [[NADP]] and these are reduced to NADPH, and then they enter the [[Calvin cycle]] and reduce the final electron acceptor, CO<sub>2</sub>.<ref>{{Cite journal |vauthors=Huang H, Ullah F, Zhou DX, Yi M, Zhao Y |date=2019 |title=Mechanisms of ROS Regulation of Plant Development and Stress Responses |journal=Frontiers in Plant Science |volume=10 |pages=800 |doi=10.3389/fpls.2019.00800 |pmc=6603150 |pmid=31293607 |doi-access=free|bibcode=2019FrPS...10..800H }}</ref> In cases where there is an ETC overload, part of the electron flow is diverted from [[ferredoxin]] to O<sub>2</sub>, forming the superoxide free radical (by the [[Mehler reaction]]). In addition, electron leakage to O<sub>2</sub> can also occur from the 2Fe-2S and 4Fe-4S clusters in the PSI ETC. However, PSII also provides electron leakage locations (QA, QB) for O<sub>2</sub>-producing O<sub>2</sub>-.<ref name="auto2">{{Cite journal |vauthors=Zhang S, Weng J, Pan J, Tu T, Yao S, Xu C |date=1 January 2003 |title=Study on the photo-generation of superoxide radicals in Photosystem II with EPR spin trapping techniques |journal=Photosynthesis Research |volume=75 |issue=1 |pages=41–48 |doi=10.1023/A:1022439009587 |pmid=16245092 |bibcode=2003PhoRe..75...41Z |s2cid=11724647}}</ref><ref>{{Cite journal |vauthors=Cleland RE, Grace SC |date=September 1999 |title=Voltammetric detection of superoxide production by photosystem II |journal=FEBS Letters |volume=457 |issue=3 |pages=348–352 |bibcode=1999FEBSL.457..348C |doi=10.1016/S0014-5793(99)01067-4 |pmid=10471806 |s2cid=1122939 |doi-access=free}}</ref> Superoxide (O<sub>2</sub>-) is generated from PSII, instead of PSI; QB is shown as the location for the generation of O<sub>2</sub>•-.<ref name="auto2" />

===Exogenous sources===
The formation of ROS can be stimulated by a variety of agents such as pollutants, [[heavy metals]],<ref name="Nachiappan" /> [[tobacco]], smoke, drugs, [[xenobiotics]], [[microplastics]], or radiation. In plants, in addition to the action of dry [[abiotic factor]]s, high temperature, interaction with other living beings can influence the production of ROS.{{citation needed|date=September 2024}}

Ionizing radiation can generate damaging intermediates through the interaction with water, a process termed [[radiolysis]]. Since water comprises 55–60% of the human body, the probability of radiolysis is quite high under the presence of ionizing radiation. In the process, water loses an electron and becomes highly reactive. Then through a three-step chain reaction, water is sequentially converted to [[hydroxyl radical]] (<sup>•</sup>OH), [[hydrogen peroxide]] (H<sub>2</sub>O<sub>2</sub>), [[superoxide radical]] (<sup>•</sup>{{chem|O|2|−}}), and ultimately [[oxygen]] (O<sub>2</sub>).{{citation needed|date=September 2024}}

The [[hydroxyl radical]] is extremely reactive and immediately removes electrons from any molecule in its path, turning that molecule into a free radical and thus propagating a chain reaction. However, [[hydrogen peroxide]] is actually more damaging to DNA than the hydroxyl radical, since the lower reactivity of hydrogen peroxide provides enough time for the molecule to travel into the nucleus of the cell, subsequently reacting with macromolecules such as DNA.{{citation needed|date=February 2019}}

In plants, the production of ROS occurs during events of abiotic stress that lead to a reduction or interruption of metabolic activity. For example, the increase in temperature, drought are factors that limit the availability of CO<sub>2</sub> due to [[stomata]]l closure, increasing the production of ROS, such as O<sub>2</sub>·- and <sup>1</sup>O<sub>2</sub> in chloroplasts.<ref>{{Cite journal |vauthors=Baniulis D, Hasan SS, Stofleth JT, Cramer WA |date=December 2013 |title=Mechanism of enhanced superoxide production in the cytochrome b(6)f complex of oxygenic photosynthesis |journal=Biochemistry |volume=52 |issue=50 |pages=8975–8983 |doi=10.1021/bi4013534 |pmc=4037229 |pmid=24298890}}</ref><ref name="auto1">{{Cite journal |vauthors=Kleine T, Leister D |date=August 2016 |title=Retrograde signaling: Organelles go networking |journal=Biochimica et Biophysica Acta (BBA) - Bioenergetics |volume=1857 |issue=8 |pages=1313–1325 |doi=10.1016/j.bbabio.2016.03.017 |pmid=26997501 |doi-access=free}}</ref> The production of <sup>1</sup>O<sub>2</sub> in chloroplasts can cause reprogramming of the expression of nucleus genes leading to [[chlorosis]] and [[apoptosis|programmed cell death]].<ref name="auto1" />
In cases of biotic stress, the generation of ROS occurs quickly and weakly initially and then becomes more solid and lasting.<ref>{{Cite journal |vauthors=Grant JJ, Loake GJ |date=September 2000 |title=Role of reactive oxygen intermediates and cognate redox signaling in disease resistance |journal=Plant Physiology |volume=124 |issue=1 |pages=21–29 |doi=10.1104/pp.124.1.21 |pmc=1539275 |pmid=10982418 |doi-access=free}}</ref> The first phase of ROS accumulation is associated with plant infection and is probably independent of the synthesis of new ROS-generating [[enzyme]]s. However, the second phase of ROS accumulation is associated only with infection by non-virulent pathogens and is an induced response dependent on increased [[mRNA]] transcription encoding enzymes.