Mitochondria diffusion into

The transport of calcium into the mitochondrion can lower external Ca2+ to levels of 1 to 0.1 jumole/1. This has, therefore, been interpreted as a basic mechanism in maintaining intracellular calcium at these levels. Only about 3 % of the calcium which passively diffuses into the cell is expelled by a calcium pump into the plasma membrane, whereas the remaining 97 % is sequestered into the mitochondria. This occurs because both processes have similar rate constants, but the total mitochondrial surface is some 30 times larger than that of the plasma membrane. This argument presupposes, however, that the calcium which enters the cell is equally available to both sets of membranes. 

Of all the intracellular organelles, the mitochondrion has been the most extensively studied with respect to the compartmentation of compounds within its boimdaries. In part, this results from the ease of separation of mitochondria from mammalian tissues (most notably the liver), as well as from the key role mitochondria play in a number of metabolic processes. The mitochondrial membrane is capable of transporting metabolites on specific transporters and of segregating metabolites from the cytosol. It is important to note that some metabolites apparently move across the mitochondrial membrane in an unspecific or non-carrier-linked manner. For example, ketone bodies, water, CO2, and oxygen appear to freely diffuse into and out of mitochondria. In the following sections we will discuss specific aspects of the transport mechanisms, followed by a more general discussion of their role in regulating major metabolic pathways. We will start with the most important result of intracellular compartmentation—oxidative phosphorylation—as viewed by the chemiosmotic theory. 

In addition to the processes described above, there still remains one further process which, at least in some cells or tissues, is required prior to the utilisation of ATP in the cytosol that is, the transport of energy within the cytosol, via a shuttle. The transport of ATP out and ADP into the mitochondrion, via the translocase, results in a high ATP/ ADP concentration ratio in the cytosol. However, a high ratio means that the actual concentration of ADP in the cytosol is low, which could result in slow diffusion of ADP from a site of ATP utilisation back to the inner mitochondrial membrane. If sufficiently slow, it could limit the rate of ATP generation. To overcome this, a process exists that transports energy within the cytosol, not by diffusion of ATP and ADP, but by the diffusion of phosphocreatine and creatine, a process known as the phosphocreatine/creatine shuttle. The reactions involved in the shuttle in muscle help to explain the significance of the process. They are ... 

Oxidizible substrates from glycolysis, fatty acid or protein catabolism enter the mitochondrion in the form of acetyl-CoA, or as other intermediaries of the Krebs cycle, which resides within the mitochondrial matrix. Reducing equivalents in the form of NADH and FADH pass electrons to complex I (NADH-ubiquinone oxidore-ductase) or complex II (succinate dehydrogenase) of the electron transport chain, respectively. Electrons pass from complex I and II to complex III (ubiquinol-cyto-chrome c oxidoreductase) and then to complex IV (cytochrome c oxidase) which accumulates four electrons and then tetravalently reduces O2 to water. Protons are pumped into the inner membrane space at complexes I, II and IV and then diffuse down their concentration gradient through complex V (FoFi-ATPase), where their potential energy is captured in the form of ATP. In this way, ATP formation is coupled to electron transport and the formation of water, a process termed oxidative phosphorylation (OXPHOS). 

As salicylate is a weak acid and has sufficient lipid solubility, it is able to diffuse across membranes. Thus, it can cross the mitochondrial membranes in its protonated form, releasing the proton into the matrix of the mitochondrion. By increasing the proton concentration, this dissipates the proton gradient and thus halts ATP production (Fig. 7.60). 

How Many Protons in a Mitochondrion Electron transfer translocates protons from the mitochondrial matrix to the external medium, establishing a pH gradient across the inner membrane (outside more acidic than inside). The tendency of protons to diffuse back into the matrix is the driving force for ATP synthesis by ATP synthase. During oxidative phosphorylation by a suspension of mitochondria in a medium of pH 7.4, the pH of the matrix has been measured as 7.7. 

Acetoacetate is another vehicle for transporting acetyl groups into the cytoplasm. This molecule, one of the end products of ketone body synthesis, is free to diffuse from the mitochondrion. When in the cytoplasm it can be activated to acetoacetyl-CoA by an ATP-dependent acetoacetyl-CoA synthetase. Edmonds group has shown that the activity of this enzyme parallels the rate of cholesterologenesis in the Uvers of animals given a variety of dietary regimes [11]. Their data also indicate that this pathway furnishes as much as 10% of the carbon required for cholesterol biosynthesis. 

Almost all cells have an active transport system to maintain nonequilibrium concentration levels of substrates. For example, in the mitochondrion, hydrogen ions are pumped into the intermembrane space of the organelle as part of producing ATP. Active transport concentrates ions, minerals, and nutrients inside the cell that are in low concentration outside. Active transport also keeps unwanted ions or other molecules that are able to diffuse through the cell membrane out of the cell. Another common active transport system class... 

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