Intermembrane space of mitochondria

BH3 domain) of the BH3-only proteins binds to other Bcl-2 family members thereby influencing their conformation. This interaction facilitates the release of cytochrome C and other mitochondrial proteins from the intermembrane space of mitochondria. Despite much effort the exact biochemical mechanism which governs this release is not yet fully understood. The release of cytochrome C facilitates the formation of the apoptosome, the second platform for apoptosis initiation besides the DISC. At the apoptosome which is also a multi-protein complex the initiator caspase-9 is activated. At this point the two pathways converge. 

Adenylate kinase (AK) is a ubiquitous monomeric enzyme that catalyzes the interconversion of AMP, ADP, and ATP. This interconversion of the adenine nucleotides seems to be of particular importance in regulating the equilibrium of adenine nucleotides in tissues, especially in red blood cells. AK has three isozymes (AK 1,2, and 3). AK 1 is present in the cytosol of skeletal muscle, brain, and red blood cells, and AK 2 is found in the intermembrane space of mitochondria of liver, kidney, spleen, and heart. AK 3, also called GTP AMP phosphotransferase, exists in the mitochondrial matrix of liver and heart. 

The (Cu,Zn)-SOD is found in the cytosol of eukaryotic cells and in the intermembrane space of mitochondria, as observed with chicken liver and also in chloroplasts, as shown with spinach and mustard leaves. A (Cu,Zn)-SOD has also been isolated from a prokaryote Photobacterium leiognathi. Could this symbiotic bacterium have borrowed the gene(s) from its host, the Pony fish, although two different subunits (Af 15,000 and 17,000) were reported for the bacterial enzyme A (Cu,Zn)-SOD was furthermore detected in Paracoccus denitrificans... 

Intrinsic (mitochondrial) pathway of caspase activation is initiated by the permeabilization of the mitochondrial outer membrane by proapoptotic members of the Bcl-2 family, resulting in a release of cytochrome c and other proteins from the intermembrane space of mitochondria into the cytosol. Cytochrome c translocation to the cytosol may follow a number of possible mechanisms. However, once in the cytosol, cytochrome c binds to apoptosis protease activating factor (Apaf-1) and in the presence of dATP or ATP facilitates Apaf-1 oligomerization and the recruitment of procaspase-9. The formation of this caspase-activating complex, termed the apoptosome, results in the activation of procaspase-9, and this in turn cleaves and activates the effector caspase-3 and -7. Activated effector caspases cleave key substrates in the cell and produce the cellular and biochemical events characteristic for apoptosis [33-35]. 

Mitochondria release not only cytochrome c but also many pro-apoptotic factors (Table 17.1). They are normally localized in the intermembrane space of mitochondria. However, except for cytochrome c and the apoptosis inducing factor (AIF), their functions in the mitochondria have not been determined or they may have no function under normal conditions. Because they are larger than 5kD, they remain inside the mitochondrion. Once the mitochondrial outer membrane is permeabi-... 

COXl 7 copper carrying molecule for the mitochondria IMS intermembrane space of mitochondria, lying between the inner and outer membranes of this organelle Metal chaperone molecule that binds a specific metal and helps insert this ion into the metal binding site of a metalloprotein... 

Mild uncoupling seems to be a first line of the mitochondrial antioxidant defence which prevents the 02 formation. If, nevertheless, some 02 is still formed, the next line of the defence is actuated. This role can be performed by cytochrome c dissolved in the solution occupying the intermembrane space of mitochondria. In fact, cytochrome c is competent in... 

This kinase is a dimer of M and B (M = muscle, B = brain) subunits produced by different structural genes. Three isozymes are possible BB (CK-1), MB (CK-2), and MM (CK-3). Another isozyme differs immunologi-cally and electrophoretically and is located in the intermembrane space of mitochondria. Tissues rich in CK-1... 

CuZnSOD is present mainly in the cytoplasm of animal cells but was also detected in lysosomes, peroxisomes, nucleus, and intermembrane space of mitochondria [1,2]. MnSOD is located in the matrix space of mitochondria [3]. However, in decapod Crustacea, which contain no CuZnSOD, MnSOD is present both in the mitochondria and in the cytosol [4]. EC-SOD is a secretory form of SOD present on the surface of many cells and outside the cells in blood plasma, lymph, ascites, and cerebrospinal fluid. However, the primary location of EC-SOD in tissues is the extracellular matrix and on cell surfaces where it is found at 20 times the concentration present in blood plasma. Tissue EC-SOD is thought to account for 90-99% of the EC-SOD of the body [5,6]. The content of EC-SOD is the highest in blood vessels, epididymis, heart, lung, kidney, testis, Sertoli and germ cells, and uterus [5, 6]. EC-SOD is also synthesized and secreted by a... 

We now know that release of cytochrome c and other proteins from the Intermembrane space of mitochondria Into the cytosol plays a major role In triggering apoptosis (Chapter 22). Certain members of the Bcl-2 family of apoptotic proteins and Ion channels localized In part to the outer mitochondrial membrane participate In this process. Yet much remains to be learned about the structure of these proteins In the mitochondrial membrane, their normal functions in cell metabolism, and the alterations that lead to apoptosis. 

Sulfite oxidase is a molybdoenzyme which catalyzes the conversion of sulfite derived from cysteine, methionine and related compounds to inorganic sulfate. Sulfite oxidase has been isolated from bovine, chicken, rat, and human liver. It is located in the intermembrane space of mitochondria, and its physiological electron acceptor is mitochondrial cytochrome c. The purified enzymes consist of two identical subunits with a molecular weight range of 55-60 kDa, containing each one atom Mo and one cytochrome b5-type heme. 

Fig. 14 Effects of tacrine and tamoxifen on mtDNA. The weak bases tacrine and tamoxifen ate protonated in the acidic intermembrane space of mitochondria and electrophoretically concentrated into the mitochondrial matrix. At these high ctmcentrations, they significantly intercalate between DNA bases, thus inhibiting mtDNA replication both directly and by inhibiting topoi-somerases. The decreased synthesis of mtDNA can lead to progressive mtDNA depletion...

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