Editing Retrograde signaling (section)

== Evolution ==
Retrograde signaling is believed to have arisen after [[endocytosis]] of the mitochondria and chloroplast billions of years ago.<ref>{{cite book | vauthors = Bevan RB, Lang BF | chapter = Mitochondrial genome evolution: the origin of mitochondria and of eukaryotes. | title = Mitochondrial Function and Biogenesis | volume = 8 | date = 2004 | pages = 1–35 | publisher = Springer | location = Berlin, Heidelberg |isbn=978-3-540-21489-2 | doi = 10.1007/b96830 | series = Topics in Current Genetics }}</ref> Originally believed to be photosynthetic bacteria, the mitochondria and chloroplast transferred some of their DNA to the membrane protected nucleus.<ref>{{cite journal | vauthors = da Cunha FM, Torelli NQ, Kowaltowski AJ | title = Mitochondrial Retrograde Signaling: Triggers, Pathways, and Outcomes | journal = Oxidative Medicine and Cellular Longevity | volume = 2015 | pages = 482582 | date = 2015 | pmid = 26583058 | pmc = 4637108 | doi = 10.1155/2015/482582 | doi-access = free }}</ref> Thus, some of the proteins required for the mitochondria or chloroplast are within the nucleus. This transfer of DNA further required a network of communication to properly respond to external and internal signals and produce requisite proteins.<ref>{{cite journal | vauthors = Whelan SP, Zuckerbraun BS | title = Mitochondrial signaling: forwards, backwards, and in between | journal = Oxidative Medicine and Cellular Longevity | volume = 2013 | pages = 351613 | date = 2013 | pmid = 23819011 | pmc = 3681274 | doi = 10.1155/2013/351613 | doi-access = free }}</ref>

=== In yeast ===
The first retrograde signaling pathways discovered in [[yeast]] is the RTG pathway.<ref>{{cite journal | vauthors = Parikh VS, Morgan MM, Scott R, Clements LS, Butow RA | title = The mitochondrial genotype can influence nuclear gene expression in yeast | journal = Science | volume = 235 | issue = 4788 | pages = 576–80 | date = January 1987 | pmid = 3027892 | doi = 10.1126/science.3027892 | bibcode = 1987Sci...235..576P }}</ref><ref name="Liu_2001">{{cite journal | vauthors = Liu Z, Sekito T, Epstein CB, Butow RA | title = RTG-dependent mitochondria to nucleus signaling is negatively regulated by the seven WD-repeat protein Lst8p | journal = The EMBO Journal | volume = 20 | issue = 24 | pages = 7209–19 | date = December 2001 | pmid = 11742997 | pmc = 125777 | doi = 10.1093/emboj/20.24.7209 }}</ref> The RTG pathway plays an important role in maintaining the metabolic homeostasis of yeast.<ref name="Liu_2001" /> Under limited resources the mitochondria must maintain a balance of [[Glutamic acid|glutamate]] for the [[citric acid cycle]].<ref>{{cite journal | vauthors = Jazwinski SM, Kriete A | title = The yeast retrograde response as a model of intracellular signaling of mitochondrial dysfunction | journal = Frontiers in Physiology | volume = 3 | pages = 139 | date = 2012 | pmid = 22629248 | pmc = 3354551 | doi = 10.3389/fphys.2012.00139 | doi-access = free }}</ref> Retrograde signaling from the mitochondria initiates production precursor molecules of glutamate to properly balance supplies within the mitochondria.<ref name="Liu_1999">{{cite journal | vauthors = Liu Z, Butow RA | title = A transcriptional switch in the expression of yeast tricarboxylic acid cycle genes in response to a reduction or loss of respiratory function | journal = Molecular and Cellular Biology | volume = 19 | issue = 10 | pages = 6720–8 | date = October 1999 | pmid = 10490611 | pmc = 84662 | doi = 10.1128/MCB.19.10.6720 }}</ref> Retrograde signaling can also act to arrest growth if problems are encountered. In ''[[Saccharomyces cerevisiae]],'' if the mitochondria fails to develop properly, they will stop growing until the issue is addressed or cell death is induced.<ref name="Liu_1999" /> This mechanism is vital to maintain homeostasis of the cell and ensure proper function of the mitochondria.<ref name="Liu_1999" />

=== In plants ===
One of the most studied retrograde signaling molecules in plants are [[reactive oxygen species]] (ROS).<ref>{{cite journal | vauthors = Maruta T, Noshi M, Tanouchi A, Tamoi M, Yabuta Y, Yoshimura K, Ishikawa T, Shigeoka S | display-authors = 6 | title = H2O2-triggered retrograde signaling from chloroplasts to nucleus plays specific role in response to stress | journal = The Journal of Biological Chemistry | volume = 287 | issue = 15 | pages = 11717–29 | date = April 2012 | pmid = 22334687 | pmc = 3320920 | doi = 10.1074/jbc.m111.292847 | doi-access = free }}</ref> These compounds, previously believed to be damaging to the cell, have since been discovered to act as a signaling molecule.<ref name="Schieber_2014">{{cite journal | vauthors = Schieber M, Chandel NS | title = ROS function in redox signaling and oxidative stress | journal = Current Biology | volume = 24 | issue = 10 | pages = R453-62 | date = May 2014 | pmid = 24845678 | pmc = 4055301 | doi = 10.1016/j.cub.2014.03.034 | bibcode = 2014CBio...24.R453S }}</ref> Reactive oxygen species are created as a by-product of aerobic respiration and act on genes involved in the stress response.<ref name="Schieber_2014" /> Depending on the stress, reactive oxygen species can act on neighboring cells to initiate a local signal.<ref name="Shapiguzov_2012">{{cite journal | vauthors = Shapiguzov A, Vainonen JP, Wrzaczek M, Kangasjärvi J | title = ROS-talk - how the apoplast, the chloroplast, and the nucleus get the message through | journal = Frontiers in Plant Science | volume = 3 | pages = 292 | date = 2012 | pmid = 23293644 | pmc = 3530830 | doi = 10.3389/fpls.2012.00292 | doi-access = free }}</ref> By doing this, surrounding cells are "primed" to react to the stress because genes involved in stress response are initiated prior to encountering the stress.<ref name="Shapiguzov_2012" /> The chloroplast can also act as a sensor for pathogen response and drought. Detection of these stresses in the cell will induce the formation of compounds that can then act on the nucleus to produce pathogen resistance genes or drought tolerance.<ref>{{cite journal | vauthors = Estavillo GM, Chan KX, Phua SY, Pogson BJ | title = Reconsidering the nature and mode of action of metabolite retrograde signals from the chloroplast | journal = Frontiers in Plant Science | volume = 3 | pages = 300 | date = 2013 | pmid = 23316207 | pmc = 3539676 | doi = 10.3389/fpls.2012.00300 | doi-access = free }}</ref>