Cation transport mitochondrial

Transport ATPases transport cations—they are ion pumps. ATPases of the F type—e. g., mitochondrial ATP synthase (see p. 142)—use transport for ATP synthesis. Enzymes of the V type, using up ATP, pump protons into lyso-somes and other acidic cell compartments (see p. 234). P type transport ATPases are particularly numerous. These are ATP-driven cation transporters that undergo covalent phosphorylation during the transport cycle. 

Weinberg, JM, Harding PG, Humes HD, Mechanisms of gentamicin-induced dysfunction of renal cortical mitochondria effects on mitochondrial monovalent cation transport. Arch Biochem Biophys, 1980,205(1) 232-39. 

The ion-binding activity of nonactin was noted in its ability to stimulate the uptake of potassium ions into mitochondria. Nonactin shows a high degree of cation specificity in regulating metabolic behavior. The translocation of sodium ion by nonactin is not as effective as that of potassium, and lithium is not translocated across mitochondrial membranes at all. The actins are very effective at enhancing the transport of cations across membranes, and are even able to mediate cation transport in carbon... 

Based on the intrinsic mitochondriotropism of dequalinium and its unique self-assembly behavior, we have developed a strategy for direct mitochondrial transfection (47-49), which involves the transport of a DNA-mitochondrial leader sequence (MLS) peptide conjugate to mitochondria using DQAsomes, the liberation of this conjugate from the cationic vector upon contact with the mitochondrial outer membrane followed by DNA uptake via the mitochondrial protein import machinery. We have demonstrated that DQAsomes fulfill all essential prerequisites for a mitochondria-specific DNA delivery system they bind and condense pDNA (24), protect it from... 

Transport systems. Partitioning of various types of molecules such as allelochemlcals into the lipid bilayer of the mitochondrial inner membrane can perturb the membrane and alter the conformation, properties, and function of components of the membranes. Unfortunately, it is not always possible to demonstrate directly the existence of carrier systems, but indirect evidence can be obtained. Alterations induced to the membrane are sometimes reflected in the osmotic behavior of mitochondria. The inner membrane is relatively impermeable to many cations, including K and H, and many solutes (31). Hence, the organelles are osmotic-ally stable under certain conditions. Indications were obtained that the allelochemlcals inhibited the action of carrier-mediated transport processes associated with the mitochondrial inner membrane (as reflected in the osmotic behavior). Responses obtained with quercetin are shown in Figure 3. Mitochondria are osmotically... 

Impetus was given to work in the field of selective cation complex-ation by the observation of Moore and Pressman (5) in 1964 that the macrocyclic antibiotic valinomycin is capable of actively transporting K+ across mitochondrial membranes. This observation has been confirmed and extended to numerous macrocyclic compounds. There is now an extensive literature on the selective complexation and transport of alkali metal ions by various macrocyclic compounds (e.g., valinomycin, mo-nactin, etc.) (2). From solution spectral (6) and crystal X-ray (7) studies we know that in these complexes the alkali metal cation is situated in the center of the inwardly oriented oxygen donor atoms. Similar results are found from X-ray studies of cyclic polyether complexes of alkali metal ions (8) and barium ion (9). These metal macrocyclic compound systems are especially noteworthy since they involve some of the few cases where alkali metal ions participate in complex ion formation in aqueous solution. 

The course of treatment also resulted in considerable positive changes in morphological and functional states of mitochondrial membranes. The passive permeability of their inner membranes for univalent cations decreased down to normal level, and transport rate of Ca ions normalized to physiological level of healthy animals. The swelling rate of mitochondria in sucrose medium increased, though remained slightly lower when compared with healthy animals. The results obtained allow us to assume that the rehabilitation of CsA-sensible pore function and membrane potential was achieved. 

Quinone type carriers perform the cotransport of two protons and two electrons (2e, 2H+ symport) [6.48, 6.49] and take part in mitochondrial and photosynthetic electron transport. Cation receptor sites such as crown ethers or cryptands bearing a quinone [6.50a] or a ferrocene [6.50b] group (see also Section 8.3.1), bind and carry cations with redox coupling through switching between a low affinity state (quinone, ferricinium) and a high affinity state (reduced quinone, ferrocene). 

Calcium levels are believed to be controlled in part at least by the uptake and release of Ca2+ from mitochondria.172"174 The capacity of mitochondria for Ca2+ seems to be more than sufficient to allow the buffering of Ca2+ at low cytosol levels. Mitochondria take up Ca2+ by an energy-dependent process either by respiration or ATP hydrolysis. It is now agreed that Ca2+ enters in response to the negative-inside membrane potential developed across the inner membrane of the mitochondrion during respiration. The uptake of Ca2+ is compensated for by extrusion of two H+ from the matrix, and is mediated by a transport protein. Previous suggestions for a Ca2+-phosphate symport are now discounted. The possible alkalization of the mitochondrial matrix is normally prevented by the influx of H+ coupled to the influx of phosphate on the H - PCV symporter (Figure 10). This explains why uptake of Ca2+ is stimulated by phosphate. Other cations can also be taken up by the same mechanism. 

Bernardi, P., 1999, Mitochondrial transport of cations Channels, exchangers and permeability transition, Physiol. Rev. 79, pp. 1127-1155... 

Within the past few years, there has been considerable progress in understanding the role played by the mitochondria in the cellular homeostasis of iron. Thus, erythroid cells devoid of mitochondria do not accumulate iron (7, 8), and inhibitors of the mitochondrial respiratory chain completely inhibit iron uptake (8) and heme biosynthesis (9) by reticulocytes. Furthermore, the enzyme ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) which catalyzes the insertion of Fe(II) into porphyrins, appears to be mainly a mitochondrial enzyme (10,11,12,13, 14) confined to the inner membrane (15, 16, 17). Finally, the importance of mitochondria in the intracellular metabolism of iron is also evident from the fact that in disorders with deranged heme biosynthesis, the mitochondria are heavily loaded with iron (see Mitochondrial Iron Pool, below). It would therefore be expected that mitochondria, of all mammalian cells, should be able to accumulate iron from the cytosol. From the permeability characteristics of the mitochondrial inner membrane (18) a specialized transport system analogous to that of the other multivalent cations (for review, see Ref. 19) may be expected. The relatively slow development of this field of study, however, mainly reflects the difficulties in studying the chemistry of iron. 

It has been generally assumed that iron is transported across biological membranes in the ferrous form and that ferric iron would have to be reduced before it can be used by the organism. Thus, based on nutritional studies it has long been recognized that Fe(II) is1 more effectively absorbed than Fe(III), and this has been attributed to differences in the thermodynamic and kinetic stability of the complexes and chelates formed by these cations (for review, see Ref. 2). The experimental proof of a transport in the ferrous form has, however, not been given until quite recently in studies of iron transport in isolated mitochondria (23) as well as in enterobacteria (33). In rat liver mitochondria we have found that Fe(III) donated from a metabolically inert water soluble complex of sucrose interacts with the respiratory chain at the level of cytochrome c (and possibly cytochrome a) (23, 32) (Figure 1 B), which has a oxidation-reduction potential of around +250 mV (34) and is localized to the outer phase of the mitochondrial inner membrane (35). 

The ions which are most frequently employed to estimate mitochondrial membrane potential are Rb in the presence of valinomycin, and lipophilic phosphonium cations. The ionophore valinomycin creates a uniport pathway for K or Rb in a variety of membranes [25]. The use of Rb enables the concentration gradient to be determined iso topically after rapid separation of the mitochondria from the medium Rb is usually considered to behave ideally in the matrix (i.e., not to be bound). Indeed, other methods of membrane potential measurement are usually referred back to the K or Rb gradient in the presence of valinomycin for their calibration. However, a disadvantage is that the ionophore will also transport K, which means that when the ionophore is added the membrane potential will tend to shift towards the value given by any K-gradient which happens to be pre-existing across the membrane. 

Since mitochondrial Ca transport is discussed in depth in Chapter 9, this section will be restrict to a brief summary of the way in which the proton circuit can be diverted into accumulating and regulating the transport of the cation, and how the permeation of weak acids is linked indirectly to net Ca transport. 

---