Mitochondria-associated membrane

Figure 2. General topological feature of PS translocation and decarboxylation in mammalian cells. PS is synthesized by PSS I and II in endoplasmic reticulum (ER) or mitochondria-associated membrane (MAM). The nascent PS is transported other membranes such as plasma membrane, nucleus, and mitochondria. The PS transported to the mitochondrial outer membrane is then translocated to the inner membrane, in which PS is converted to PE by PS decarboxylase (PSD). The PE formed in mitochondria is dynamic and can be exported to other organelles for membrane biogenesis.

Rusinol, A.E., Cui, Z, Chen, M.H., and Vance, J.E., 1994, A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins. J. Biol. Chem., 269 27494-27502. 

Shiao, Y.J., Lupo, G., and Vance, J.E., 1995, Evidence that phosphatidylserine is imported into mitochondria via a mitochondria-associated membrane and that the majority of mitochondrial phosphatidylethanolamine is derived from decarboxylation of phosphatidylserine./. Bio/. Chem. 270 11190-11198. 

Bionda C, Portoukalian J, Schmitt D, Rodriguez-Lafrasse C, Ardail D. Subcellular compartmentalization of ceramide metabolism MAM (mitochondria-associated membrane) and/or mitochondria Biochem J 2004 382 527-533. 

S.J. Stone and J.E. Vance, Phosphatidyl-serine synthase-1 and -2 are localized to mitochondria-associated membranes, J. Bid. Chem., 2000, 275, 34534-34540. 

More detailed studies indicate that such mitochondrial fractions are likely to contain another resolvable compartment, the mitochondria-associated membrane (MAM) that appears to be a specialized domain of the ER (J.E. Vance, 1990). Evidence obtained using CHO-Kl cells (Y. Shiao, 1995) indicates that nascent PE (made via CDP-ethanolamine) is transported to the MAM but not to the inner mitochondrial membrane. It remains unclear whether some of this PE is transported to the outer mitochondrial membrane. The results are consistent with little import of PE derived from ethanolamine into mitochondria. Furthermore, yeast mutants lacking a functional allele for PS decarboxylase 1 (psdIA strains) are markedly deficient in mitochondrial PE (P.J. Trotter, 1995). The reduced PE in mitochondria cannot be fully restored by PE synthesized in the ER from an ethanolamine precursor, or that made in the Golgi or vacuole by PS decarboxylase 2 (R. Bimer, 2001 M. Storey, 2001). These latter findings clearly demonstrate that there is compartmentation and restricted transport of different pools of PE within cells. 

Because Rlil homologs have been found only in archaebacteria (reviewed in Tachezy and Dolezal 2007), it is hypothesized that Rlil and other components of cytosolic translation machinery are derived from them. Therefore, we propose that the intimate association of the relic mitochondrion, of eubacterial origin, with its associated membranes is a structural reflection of the cell s attempt to facilitate efficient ribosome biogenesis and translation initiation following reductive evolution of the organelle (Keeling 2004 ... 

Haresh K, Suresh K, Khairul Anus A, Saminathan S (1999) Isolate resistance of Blastocystis hominis to metronidazole. Trop Med Int Health 4 274-277 Inui H, Ono K, Miyatake K, Nakano Y, Kitaoka S (1987) Purification and characterization of pyruvate NADP+ oxidoreductase in Euglena gracilis. J Biol Chem 262 9130-9135 Keithly JS, Langreth SG, Buttle KF, Mannella CA (2005) Electron tomographic and ultra-structural analysis of the Cryptosporidium parvum relict mitochondrion, its associated membranes, and organelles. J Eukaryot Microbiol 52 132-140 Kurland CG, Andersson SGE (2000) Origin and evolution of the mitochondrial proteome. Micro Mol Biol Rev 64 786-820... 

Keithly JS, Langreth SG, Buttle KF, Mannella CA (2005) Electron tomographic and ultrastruc-tural analysis of the Cryptosporidium parvum relict mitochondrion, its associated membranes and organelles. J Eukaryot Microbiol 52 132-140 Knight J (2004) Giardia not so special, after all Nature 429 236-237... 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

Subsurface cisternae are a system of smooth, membrane-bound, flattened cisternae that can be found in many neurons. These structures, referred to as hypolemmal cisternae by Palay and Chan-Palay [1], abut the plasmalemma of the neuron and constitute a secondary membranous boundary within the cell. The distance between these cisternae and the plasmalemma is usually 10-12 nm and, in some neurons, such as the Purkinje cells, a mitochondrion may be found in close association with the innermost leaflet. Similar cisternae have been described beneath synaptic complexes, but their functional significance is not... 

FIG. 4. Ultrastructure of vascular smooth muscle of the rabbit inferior vena cava revealed with electron microscopy. Serial cross-sections of VSMCs are shown in series 1 (panel A—D) and series 2 (panel E—G). Series 1 illustrates the close spatial apposition between the superficial SR sheet and the PM with the apices of the caveolae perforating through the superficial SR sheets to come into contact with the bulk cytoplasm. The membranes of the PM (dotted line) and the SR (solid line) in panel A-D are outlined to the right of the respective panels. The close apposition between the superficial SR sheet, the PM and the neck region of the caveolae creates a narrow and expansive restricted space. Series 2 illustrates the perpendicular sheets of SR, which appear to arise from the superficial SR sheets. Mitochondria also come into close contact with the perpendicular SR sheets. Panel H contains a stylized illustration of the close association between the superficial SR sheet, which is continuous with the perpendicular sheet, the perforating caveolae (C), the PM and a mitochondrion (M). Panel I shows calyculin-A mediated dissociation of the superficial SR sheets from the PM (see arrows). The black scale bar indicated represents 200 nm of distance. 

Mitochondria arise by division and growth of preexisting mitochondria. Because they synthesize only a few proteins and RNA molecules, they must import many proteins and other materials from the cytoplasm. A mitochondrion contains at least 100 proteins that are encoded by nuclear genes.50,50a The mechanisms by which proteins are taken up by mitochondria are complex and varied. Many of the newly synthesized proteins carry, at the N terminus, presequences that contain mitochondrial targeting signals51-53 (Chapter 10). These amino acid sequences often lead the protein to associate with receptor proteins on the outer mitochondrial membrane and subsequently to be taken up by the mitochondria. While the targeting sequences are usually at the N terminus of a polypeptide, they are quite often internal. The N-terminal sequences are usually removed by action of the mitochondrial processing peptidase (MPP) in... 

Mitochondria are intracellular centers for aerobic metabolism. They are cell organelles that are identified by well-defined structural and biochemical properties. In morphological terms, mitochondria are relatively large particles that are characterized by the presence of two membranes, a smooth outer membrane that is permeable to most important metabolites and an inner membrane that has unique transport properties. The inner membrane is highly folded, which serves to increase its surface area. Figure E10.1, which shows the structure of a typical mitochondrion, divides the organelle into four major components inner membrane, outer membrane, intermembrane space, and the matrix. These regions are associated with different and... 

Therefore, as a mitochondrion membrane is broken, it somewhat disrupts communications between two conjugated reactions (respiration and phosphorylation). Hence, as expected, phosphorylation is completely terminated. This kinetic behavior of the system, both unclear and unusual at first glance, is quite logical, and is associated with the membrane origin of the ATP synthesis. 

In the previous section we mentioned the ADP/ATP transporter, and it is also shown in Figure 17.2. This system allows the export of ATP and import of ADP. Because ATP and ADP have net charges of -4 and -3, respectively, at pH 7, the transport is not electroneutral and must occur at the expense of the membrane potential. Atractyloside and bongkrekic acid are inhibitors of this system, the former binding to the ADP binding site of the porter and the latter to the ATP site. Associated with ADP/ATP transport is the transport of P which must enter the mitochondrion to participate in ATP formation. Several systems for transport-... 

A FIGURE 18-1 Overview of synthesis of major membrane lipids and their movement into and out of cells. Membrane lipids (e.g., phospholipids, cholesterol) are synthesized through complex multienzyme pathways that begin with sets of water-soluble enzymes and intermediates in the cytosol (D) that are then converted by membrane-associated enzymes into water-insoluble products embedded in the membrane (B), usually at the interface between the cytosolic leaflet of the endoplasmic reticulum (ER) and the cytosol. Membrane lipids can move from the ER to other organelles (H), such as the Golgi apparatus or the mitochondrion, by either vesicle-mediated or other poorly defined mechanisms. Lipids can move into or out of cells by plasma-membrane transport proteins or by lipoproteins. Transport proteins similar to those described in Chapter 7 that move lipids (0) include sodium-coupled symporters that mediate import CD36 and SR-BI superfamily proteins that can mediate... 

Mitochondria and cell death Although oxidative phosphorylation is a mitochondrial process, most ATP utilization occurs outside of the mitochondrion. ATP synthesized from oxidative phosphorylation is actively transported from the matrix to the intermembrane space by adenine nucleotide translocase (ANT). Porins form voltage-dependent anion channels (VDAC) through the outer mitochondrial membrane for the diffusion of H2O, ATP metabolites, and other ions. Under certain types of stress, ANT, VDAC, and other proteins form a nonspecific open channel known as the mitochondrial permeability transition pore. This pore is associated with events that lead rapidly to necrotic cell death. 

A second very important eukaryotic organelle is the mitochondrion, which, like the nucleus, has a double membrane (Figure 1.13). The outer membrane has a fairly smooth surface, but the inner membrane exhibits many folds called cristae. The space within the inner membrane is called the matrix. Oxidation processes that occur in mitochondria yield energy for the cell. Most of the enzymes responsible for these important reactions are associated with the inner mitochondrial membrane. Other enzymes needed for oxidation reactions, as well as DNA that differs from that found in the nucleus, are found in the internal mitochondrial matrix. Mitochondria also contain ribosomes similar to those found in bacteria. Mitochondria are approximately the size of many bacteria, typically about 1 pm in diameter and 2 to 8 pm in length. In theory, they may have arisen from the absorption of aerobic bacteria by larger host cells. 

Many particles pass through the membrane of a cell with the electrochemical energy gradient, but some against it. Adenosin triphosphate (ATP) is thought to provide the energy for this latter occurrence. An important biochemical reaction is, then, the endothermic formation of ATP by the phosphorylation process. The enzymes which are associated with this are found in the subcellular unit known as the mitochondrion. Electrochemical reactions may function here. 

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