Does released cytochrome get degraded after it binds to apaf-1 and does it form the apoptosome? I also heard from my supervisor that it goes back to the mitochondrial membrane, which seems counterintuitive for me. We want to detect the time points for cytochrome c release and examine how long cytochrome c can be detected in the cytoplasm.
Hi Helen,
Very interesting question and has not been studied in much detail. The reason is obvious, as intrinsinc apoptotic pathway is initiated by the release of Cyt C from mitochondria. I have observed that Cyt C release increases with time after the apoptotic cascade is initiated, due to the increased stress (Oxidative stress). Since Cell is finally destined to die, i do not think it will trans-locate back to mitochondria.
Cytochrome c can be reduced or oxidized.
With the oxidized form being pro-apoptotic, one can postulate that there is cytochrome c recycling taking place (reduction), that may limit cytochrome c action within cells.
See the interesting work by Guy C Brown in 2008. doi:10.1016/j.bbabio.2008.03.024
When I was a postdoc back in late 90's, some interesting papers came out that argued for reversibility of both cytochrome c release from mitochondria and changes in mitochondrial transmembrane potential during apoptosis. In particular Caroline Dive's group made significant claims. I have attached their paper wish was published in Blood in 1998. I have not followed her publications etc since then. It is worth looking at them.
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