I am looking for the possible mechanisms involving in decreasing potential of mitochondrial membrane and causes the release of cytochrome c to the cytoplasm which then activate the caspase cascade and apoptosis.
There is a very precise and redundant mechanism of balance between pro and anti apoptotic proteins that act on the mitochondrial membrane. The BCL-2 family of proteins with its anti-apoptotic component and the BH3 only pro-apoptotic component represent a very good example of this balance.
BH3-only BCL-2 family proteins are effectors of canonical mitochondrial apoptosis. They discharge their pro-apoptotic functions through BH1-3 pro-apoptotic proteins such as BAX and BAK, while their activity is suppressed by BH1-4 anti-apoptotic BCL-2 family members. The precise mechanism by which BH3-only proteins mediate apoptosis remains unresolved. The existing data are consistent with three mutually non-exclusive models (1) displacement of BH1-3 proteins from complexes with BH1-4 proteins; (2) direct interaction with and conformational activation of BH1-3 proteins; and (3) membrane insertion and membrane remodeling. The BH3-only proteins appear to play critical roles in restraining cancer and inflammatory diseases such as rheumatoid arthritis. Molecules that mimic the effect of BH3-only proteins are being used in treatments against these diseases. The cell death activity of a subclass of BH3-only members (BNIP3 and BNIP3L) is linked to cardiomyocyte loss during heart failure. In addition to their established role in apoptosis, several BH3-only members also regulate diverse cellular functions in cell-cycle regulation, DNA repair and metabolism. Several members are implicated in the induction of autophagy and autophagic cell death, possibly through unleashing of the BH3-only autophagic effector Beclin 1 from complexes with BCL-2/BCL-xL.
I am not sure what exactly you are looking for but there are few very good apoptosis reviews available as full text articles here at ResearchGate
https://www.researchgate.net/publication/281708880_Molecular_Mechanisms_of_Apoptosis_and_Roles_in_Cancer_Development_and_Treatment
https://www.researchgate.net/publication/308080496_Mitochondrial_ROS_and_Apoptosis
Article Molecular Mechanisms of Apoptosis and Roles in Cancer Develo...
Chapter Mitochondrial ROS and Apoptosis
The mechanisms involved are several, also remember oxidative stress by the accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), with consequent damage to biological macromolecules, particularly the lipids of the cell membrane.
The bax/bcl2 ratio if gets disturbed, it causes MMP depolarization that results cytochrome c release
thanks everybody...actually i got mitochondrial membrane dysfunction but not remarkable change in ROS thats why i am asking about any other mechanism which may be involve..i also got bax/bcl2 ratio changed by it is downstream to mito dysfunction... i need any upstream pathway
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