Diferenzas entre revisións de «Citocromo c»

The sustained elevation in [[calcium]] levels precedes cyt ''c'' release from the mitochondria. The release of small amounts of cyt ''c'' leads to an interaction with the [[Inositol triphosphate receptor|IP3 receptor]] (IP3R) on the [[endoplasmic reticulum]] (ER), causing ER calcium release. The overall increase in calcium triggers a massive release of cyt ''c'', which then acts in the positive feedback loop to maintain ER calcium release through the IP3Rs.<ref name="pmid14608362">{{cite journal | author = Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH | title = Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis | journal = Nat. Cell Biol. | volume = 5 | issue = 12 | pages = 1051–61 |date=December 2003 | pmid = 14608362 | doi = 10.1038/ncb1063 }}</ref> This explains how the ER calcium release can reach cytotoxic levels. This release of cytochrome c in turn activates [[caspase 9]], a cysteine [[protease]]. Caspase 9 can then go on to activate [[caspase 3]] and [[caspase 7]], which are responsible for destroying the cell from within.
 
== Localización extramitocondrial ==
== Extramitochondrial localization ==
 
Cytochrome c is widely believed to be localized solely in the mitochondrial intermembrane space under normal physiological conditions.<ref name="pmid9242927">{{cite journal | author = Neupert W | title = Protein import into mitochondria | journal = Annu. Rev. Biochem. | volume = 66 | issue = | pages = 863–917 | year = 1997 | pmid = 9242927 | doi = 10.1146/annurev.biochem.66.1.863 }}</ref> The release of cytochrome-c from mitochondria to the cytosol, where it activates the [[caspase]] family of [[proteases]] is believed to be primary trigger leading to the onset of apoptosis.<ref name="pmid9558479">{{cite journal | author = Kroemer G, Dallaporta B, Resche-Rigon M | title = The mitochondrial death/life regulator in apoptosis and necrosis | journal = Annu. Rev. Physiol. | volume = 60 | issue = | pages = 619–42 | year = 1998 | pmid = 9558479 | doi = 10.1146/annurev.physiol.60.1.619 }}</ref> However, detailed immunoelectron microscopic 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 | author = Soltys BJ, Andrews DW, Jemmerson R, Gupta RS | title = Cytochrome-C localizes in secretory granules in pancreas and anterior pituitary | journal = Cell Biol. Int. | volume = 25 | issue = 4 | pages = 331–8 | year = 2001 | pmid = 11319839 | doi = 10.1006/cbir.2000.0651 }}</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 [[vacuoles]] and in the acinar [[Lumen_(anatomy)|lumen]]. The extramitochondrial localization of cytochrome c was shown to be specific as it was completed abolished upon adsorption of the primary antibody with the purified cytochrome c.<ref name="Soltys_2001" /> The presence of cytochrome-c outside of mitochondria at specific location under normal physiological conditions raises important questions concerning its cellular function and translocation mechanism.<ref name="Soltys_2001" /> Besides cytochrome c, extramitochondrial localization has also been observed for large numbers of other proteins including those encoded by mitochondrial DNA.<ref name="pmid18575266">{{cite journal | author = Gupta RS, Ramachandra NB, Bowes T, Singh B | title = Unusual cellular disposition of the mitochondrial molecular chaperones Hsp60, Hsp70 and Hsp10 | journal = Novartis Found. Symp. | volume = 291 | issue = | pages = 59–68; discussion 69–73, 137–40 | year = 2008 | pmid = 18575266 | doi = }}</ref><ref name="pmid16133117">{{cite journal | author = Sadacharan SK, Singh B, Bowes T, Gupta RS | title = Localization of mitochondrial DNA encoded cytochrome c oxidase subunits I and II in rat pancreatic zymogen granules and pituitary growth hormone granules | journal = Histochem. Cell Biol. | volume = 124 | issue = 5 | pages = 409–21 |date=November 2005 | pmid = 16133117 | doi = 10.1007/s00418-005-0056-2 }}</ref><ref name="Soltys_2000">{{cite journal | author = Soltys BJ, Gupta RS | title = Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from an evolutionary perspective | journal = Int. Rev. Cytol. | volume = 194 | issue = | pages = 133–96 | year = 2000 | pmid = 10494626 | doi = }}</ref> This raises the possibility about existence of yet unidentified specific mechanisms for protein translocation from mitochondria to other cellular destinations.<ref name="Soltys_2000" /><ref name="pmid10322429">{{cite journal | author = Soltys BJ, Gupta RS | title = Mitochondrial-matrix proteins at unexpected locations: are they exported? | journal = Trends Biochem. Sci. | volume = 24 | issue = 5 | pages = 174–7 |date=May 1999 | pmid = 10322429 | doi = }}</ref>
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