Cytochrome C synthesis and apoptosis

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jrebers
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Cytochrome C synthesis and apoptosis

Post by jrebers » Mon Nov 12, 2007 3:57 pm

Release of cytochrome C from the intermembrane space of mitochondria induces apoptosis, by forming a cytochrome C/Apaf1 complex that activates a caspase cascade. Why doesn't cytochrome C activate this pathway while it is being synthesized in the cytosol? My best guess is that the newly synthesized cytochrome C binds to the TOM1 import complex in the mitochondrial outer membrane faster than it binds to Apaf1, but I couldn't find any research or review articles addressing this. If anyone knows the answer to this question or can point me to some articles, I'd appreciate it.

Thanks!

jrebers
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Post by jrebers » Sat Nov 17, 2007 3:30 pm

I found the answer to this question elsewhere. There were enough people checking out the question I thought the answer would be of general interest. Cytochrome C is synthesized as an apoprotein and needs a heme group added to be functional for either electron transport or to combine with Apaf-1 to induce apoptosis. The heme group is added in the mitochondrion. It turns out that apocytochrome C, the form found immediately after synthesis in the cytosol, actively inhibits apoptosis. See:
Martin AG, Nguyen J, Wells JA, Fearnhead HO.
Apo cytochrome c inhibits caspases by preventing apoptosome formation.
Biochem Biophys Res Commun. 2004 Jul 2;319(3):944-50.
PMID: 15184073 [PubMed - indexed for MEDLINE]

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