Editing Mitochondrion (section)

===Uptake, storage and release of calcium ions===
[[File:Chondrocyte- calcium stain.jpg|right|thumb|400 px|[[Transmission electron microscope|Transmission]] [[Micrograph|electron micrograph]] of a [[chondrocyte]], stained for calcium, showing its nucleus (N) and mitochondria (M)]]
The concentrations of free calcium in the cell can regulate an array of reactions and is important for [[signal transduction]] in the cell. Mitochondria can transiently [[Calcium storage|store calcium]], a contributing process for the cell's homeostasis of calcium.<ref name="Santulli-2015c">{{cite journal | vauthors = Santulli G, Xie W, Reiken SR, Marks AR | title = Mitochondrial calcium overload is a key determinant in heart failure | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 36 | pages = 11389–11394 | date = September 2015 | pmid = 26217001 | pmc = 4568687 | doi = 10.1073/pnas.1513047112 | doi-access = free | bibcode = 2015PNAS..11211389S }}</ref>
<ref name="Siegel-1999">{{cite book | veditors = Siegel GJ, Agranoff BW, Fisher SK, Albers RW, Uhler MD |title=Basic Neurochemistry |edition=6 |year=1999 |isbn=978-0397518203 |publisher=Lippincott Williams & Wilkins }}</ref> Their ability to rapidly take in calcium for later release makes them good "cytosolic buffers" for calcium.<ref name="Rossier-2006"/><ref>{{cite journal | vauthors = Brighton CT, Hunt RM | title = Mitochondrial calcium and its role in calcification. Histochemical localization of calcium in electron micrographs of the epiphyseal growth plate with K-pyroantimonate | journal = Clinical Orthopaedics and Related Research | volume = 100 | issue = 5 | pages = 406–416 | date = May 1974 | pmid = 4134194 | doi = 10.1097/00003086-197405000-00057 }}</ref><ref>
{{cite journal | vauthors = Brighton CT, Hunt RM | title = The role of mitochondria in growth plate calcification as demonstrated in a rachitic model | journal = The Journal of Bone and Joint Surgery. American Volume | volume = 60 | issue = 5 | pages = 630–639 | date = July 1978 | pmid = 681381 | doi = 10.2106/00004623-197860050-00007 }}</ref> The endoplasmic reticulum (ER) is the most significant storage site of calcium,<ref name="Santulli-2015b"/> and there is a significant interplay between the mitochondrion and ER with regard to calcium.<ref>{{cite journal | vauthors = Pizzo P, Pozzan T | title = Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics | journal = Trends in Cell Biology | volume = 17 | issue = 10 | pages = 511–517 | date = October 2007 | pmid = 17851078 | doi = 10.1016/j.tcb.2007.07.011 }}</ref> The calcium is taken up into the [[mitochondrial matrix|matrix]] by the [[mitochondrial calcium uniporter]] on the [[inner mitochondrial membrane]].<ref name="Miller-1998">{{cite journal | vauthors = Miller RJ | title = Mitochondria - the Kraken wakes! | journal = Trends in Neurosciences | volume = 21 | issue = 3 | pages = 95–97 | date = March 1998 | pmid = 9530913 | doi = 10.1016/S0166-2236(97)01206-X }}</ref> It is primarily driven by the mitochondrial [[membrane potential]].<ref name="Siegel-1999"/> Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways.<ref name="Miller-1998"/> This can initiate calcium spikes or calcium waves with large changes in the membrane potential. These can activate a series of [[second messenger system]] proteins that can coordinate processes such as [[Synaptic vesicle|neurotransmitter release]] in nerve cells and release of [[hormone]]s in endocrine cells.<ref name="Santulli-2015a">{{cite journal | vauthors = Santulli G, Pagano G, Sardu C, Xie W, Reiken S, D'Ascia SL, Cannone M, Marziliano N, Trimarco B, Guise TA, Lacampagne A, Marks AR | title = Calcium release channel RyR2 regulates insulin release and glucose homeostasis | journal = The Journal of Clinical Investigation | volume = 125 | issue = 5 | pages = 1968–1978 | date = May 2015 | pmid = 25844899 | pmc = 4463204 | doi = 10.1172/JCI79273 }}</ref>

Ca{{sup|2+}} influx to the mitochondrial matrix has recently been implicated as a mechanism to regulate respiratory [[bioenergetics]] by allowing the electrochemical potential across the membrane to transiently "pulse" from ΔΨ-dominated to pH-dominated, facilitating a reduction of [[oxidative stress]].<ref>{{cite journal | vauthors = Schwarzländer M, Logan DC, Johnston IG, Jones NS, Meyer AJ, Fricker MD, Sweetlove LJ | title = Pulsing of membrane potential in individual mitochondria: a stress-induced mechanism to regulate respiratory bioenergetics in Arabidopsis | journal = The Plant Cell | volume = 24 | issue = 3 | pages = 1188–1201 | date = March 2012 | pmid = 22395486 | pmc = 3336130 | doi = 10.1105/tpc.112.096438 | bibcode = 2012PlanC..24.1188S }}</ref> In neurons, concomitant increases in cytosolic and mitochondrial calcium act to synchronize neuronal activity with mitochondrial energy metabolism. Mitochondrial matrix calcium levels can reach the tens of micromolar levels, which is necessary for the activation of [[isocitrate dehydrogenase]], one of the key regulatory enzymes of the [[Krebs cycle]].<ref>{{cite journal | vauthors = Ivannikov MV, Macleod GT | title = Mitochondrial free Ca²⁺ levels and their effects on energy metabolism in Drosophila motor nerve terminals | journal = Biophysical Journal | volume = 104 | issue = 11 | pages = 2353–2361 | date = June 2013 | pmid = 23746507 | pmc = 3672877 | doi = 10.1016/j.bpj.2013.03.064 | bibcode = 2013BpJ...104.2353I }}</ref>