This event triggers the release of pro-apoptotic proteins, including cytochrome C, from the mitochondrial intermembrane space
to the cytosol where they activate caspases and endonucleases that initiates apoptosis.
After treatment of cells with apoptotic agents including H202, cytochrome c is released from mitochondrial intermembrane space
and binds to the apoptosis protease activation factor (APAf-1) to forms an apoptosome complex.
In response to apoptotic stimuli, several proapoptotic proteins are released into the cytoplasm from the mitochondrial intermembrane space, including Smac/DIABLO, apoptosis-inducing factor (AIF), high temperature requirement protein A2 (HtrA2/Omi), cytochrome c, and endonuclease G.
HtrA2/Omi is a 37-kDa serine protease located in the mitochondrial intermembrane space that plays an important physiologic role in mitochondrial homeostasis.
The CK reaction catalysed by its mitochondrial isoenzyme MtCK in the mitochondrial intermembrane space
is directed towards the synthesis of another high-energy phosphorus compound, phosphocreatine (PCr), which is liberated into the cytoplasm through the mitochondrial voltage-dependent anion selective channels (VDAC) leaving another reaction product, ADP, for further ATP resynthesis in the mitochondrial matrix.
These results can be explained on the basis of findings of Chattopadhya et al , which showed that I/R injury inhibits Bcl-2 gene expression resulting and bind to the "permeability transition pore" of mitochondrial membrane inducing loss of selective ion permeability which results in release into the cytosol intermembrane space
contents including cytochrome c and apoptosis-inducing factor (AIF).
Complex I also has proton-transporting activity over the inner mitochondrial membrane to the intermembrane space
The Disulfide Relay of the Intermembrane Space
of Mitochondria: An Oxygen-Sensing System?
Apoptosis is characterized by several biochemical criteria, including changes in mitochondrial membrane permeability, caspase activation, internucleosomal DNA cleavage, release of intermembrane space
mitochondrial proteins in the formation of apoptotic bodies, chromatin fragmentation, shrinkage of cells and bleb formation (Kim et al.
The intrinsic pathway involves an increase of outer mitochondrial membrane permeability that leads to the release of various proteins from the intermembrane space
into the cytoplasm, such as cytochrome c and DNaseG (Green and Reed 1998; Tsujimoto and Shimizu 2007).
One of the most reliable methods of assessing muscular damage is to check for increases in blood serum levels of creatine kinase (CK), which is located in the sarcolemma and mitochondrial intermembrane space
of healthy muscle cells.
Additionally, it depends on the optimal activity and integrity of the respiratory chain (complexes I, III and IV), which extrudes protons from the mitochondrial matrix toward the intermembrane space