Editing Cytochrome c (section)

== Extramitochondrial localisation ==

Cytochrome c is widely believed to be localised solely in the mitochondrial intermembrane space under normal physiological conditions.<ref name="pmid9242927">{{Cite journal |vauthors=Neupert W |year=1997 |title=Protein import into mitochondria |journal=Annual Review of Biochemistry |volume=66 |pages=863–917 |doi=10.1146/annurev.biochem.66.1.863 |pmid=9242927}}</ref> The release of cytochrome c from mitochondria to the cytosol, where it activates the [[caspase]] family of [[proteases]], is believed to be the primary trigger leading to the onset of apoptosis.<ref name="pmid9558479">{{Cite journal |vauthors=Kroemer G, Dallaporta B, Resche-Rigon M |year=1998 |title=The mitochondrial death/life regulator in apoptosis and necrosis |journal=Annual Review of Physiology |volume=60 |pages=619–42 |doi=10.1146/annurev.physiol.60.1.619 |pmid=9558479}}</ref> Measuring the amount of cytochrome c leaking from mitochondria to cytosol, and out of the cell to culture medium, is a sensitive method to monitor the degree of apoptosis.<ref name="pmid24054573">{{Cite journal |vauthors=Loo JF, Lau PM, Ho HP, Kong SK |date=October 2013 |title=An aptamer-based bio-barcode assay with isothermal recombinase polymerase amplification for cytochrome-c detection and anti-cancer drug screening |journal=[[Talanta]] |volume=115 |pages=159–65 |doi=10.1016/j.talanta.2013.04.051 |pmid=24054573}}</ref><ref name="pmid12815469">{{Cite journal |vauthors=Waterhouse NJ, [[Joseph Trapani (immunologist)|Trapani JA]] |date=July 2003 |title=A new quantitative assay for cytochrome c release in apoptotic cells |journal=[[Cell Death and Differentiation]] |volume=10 |issue=7 |pages=853–5 |doi=10.1038/sj.cdd.4401263 |pmid=12815469 |doi-access=free}}</ref>  However, detailed immuno-electronmicroscopic studies with rat tissues sections employing cytochrome c specific antibodies provide compelling evidence that cytochrome c under normal cellular conditions is also present at extramitochondrial locations.<ref name="Soltys_2001">{{Cite journal |vauthors=Soltys BJ, Andrews DW, Jemmerson R, Gupta RS |year=2001 |title=Cytochrome-C localises in secretory granules in pancreas and anterior pituitary |journal=Cell Biology International |volume=25 |issue=4 |pages=331–8 |doi=10.1006/cbir.2000.0651 |pmid=11319839 |s2cid=2106599}}</ref> In pancreatic acinar cells and the [[anterior pituitary]], strong and specific presence of cytochrome c was detected in [[zymogen]] granules and in [[growth hormone]] granules, respectively. In the pancreas, cytochrome c was also found in condensing [[vacuole]]s and in the acinar [[Lumen (anatomy)|lumen]]. The extramitochondrial localisation of cytochrome c was shown to be specific as it was completely abolished upon adsorption of the primary antibody with purified cytochrome c.<ref name="Soltys_2001" /> Besides cytochrome c, extramitochondrial localisation has also been observed for large numbers of other proteins including those encoded by mitochondrial DNA.<ref name="pmid18575266">{{Cite book |title=The Biology of Extracellular Molecular Chaperones |vauthors=Gupta RS, Ramachandra NB, Bowes T, Singh B |year=2008 |isbn=978-0-470-75403-0 |veditors=Chadwick D, Goode J |series=Novartis Foundation Symposia |volume=291 |pages=59–68; discussion 69–73, 137–40 |chapter=Unusual Cellular Disposition of the Mitochondrial Molecular Chaperones Hsp60, Hsp70 and Hsp10 |doi=10.1002/9780470754030.ch5 |pmid=18575266}}</ref><ref name="pmid16133117">{{Cite journal |vauthors=Sadacharan SK, Singh B, Bowes T, Gupta RS |date=November 2005 |title=Localisation of mitochondrial DNA encoded cytochrome c oxidase subunits I and II in rat pancreatic zymogen granules and pituitary growth hormone granules |journal=[[Histochemistry and Cell Biology]] |volume=124 |issue=5 |pages=409–21 |doi=10.1007/s00418-005-0056-2 |pmid=16133117 |s2cid=24440427}}</ref><ref name="Soltys_2000">{{Cite book |title=Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from an evolutionary perspective |vauthors=Soltys BJ, Gupta RS |year=2000 |isbn=978-0-12-364598-2 |series=International Review of Cytology |volume=194 |pages=133–96 |doi=10.1016/s0074-7696(08)62396-7 |pmid=10494626}}</ref> This raises the possibility of the existence of yet-unidentified specific mechanisms for protein translocation from mitochondria to other cellular destinations.<ref name="Soltys_2000" /><ref name="pmid10322429">{{Cite journal |vauthors=Soltys BJ, Gupta RS |date=May 1999 |title=Mitochondrial-matrix proteins at unexpected locations: are they exported? |journal=[[Trends in Biochemical Sciences]] |volume=24 |issue=5 |pages=174–7 |doi=10.1016/s0968-0004(99)01390-0 |pmid=10322429}}</ref>