Ion transport, in mitochondria

Penttila, T. and Wikstrom, M. (1981) In Vectorial Reactions in Electron and Ion Transport in Mitochondria and Bacteria (Palmieri, F. et ah, eds.) pp. 71-80, Elsevier/North-Holland, Amsterdam. 

Augustin W, Gellerich F, Wiswedel I, et al. 1979. Inhibition of cation efflux by antioxidants during oscillatory ion transport in mitochondria. FEBS Lett 107(1) 151-154. 

Schuurmans JJ, Peters ALJ, Leeuwerik FJ and Kraayenhof R (1981) On the association of electrical events with the synthesis and hydrolysis of ATP in photosynthetic membranes. In Palmiere F et al., ed. Vectorial reactions in electron and ion transport in mitochondria and bacteria, pp. 359-369, Elsevier, Amsterdam. 

Rugolo, M., Pistocchi, R., and Zannoni, D., Calcium ion transport in higher plant mitochondria (Helianthus tuberosus), Physiol. Plant., 79, 297-302, 1990. 

In 1964, Moore and Pressman [16] discovered that vaiinomydn induces K" -uptake in mitochondria. By various methods it was then demonstrated that in alcoholic solution the depsipeptide forms very stable complexes with K, Rb" and Cs -ions. Since then the investigation of mechanisms by which certain substances facilitate ion transport in lipid membranes has developed into a major field in biophysics. Besides the carrier transport mentioned here, there also exists a channel mechanism. 

H.Rottenberg, S.R.Caplan and A.Essig, A thermodynamic appraisal of oxidative phosphorylation with special reference to ion transport by mitochondria, in Membranes and ion transport, vol.l, E.E.Bittar ed., Wiley Interscience, London (1970). 

FIGURE 8 ATP, ADR and Pj transport in mitochondria. ATP is formed inside mitochondria. Most of the ATP is exported to the cytoplasm where it is cleaved to ADP and Pj. The mitochondrial inner membrane contains specific proteins that mediate not only ATP release coupled to ADP uptake, but also Pj uptake linked to hydroxide ion (OH ) release. 

Mechanistic studies have shown that TBT and certain other forms of trialkyltin have two distinct modes of toxic action in vertebrates. On the one hand they act as inhibitors of oxidative phosphorylation in mitochondria (Aldridge and Street 1964). Inhibition is associated with repression of ATP synthesis, disturbance of ion transport across the mitochondrial membrane, and swelling of the membrane. Oxidative phosphorylation is a vital process in animals and plants, and so trialkyltin compounds act as wide-ranging biocides. Another mode of action involves the inhibition of forms of cytochrome P450, which was referred to earlier in connection with metabolism. This has been demonstrated in mammals, aquatic invertebrates and fish (Morcillo et al. 2004, Oberdorster 2002). TBTO has been shown to inhibit P450 activity in cells from various tissues of mammals, including liver, kidney, and small intestine mucosa, both in vivo and in vitro (Rosenberg and Drummond 1983, Environmental Health Criteria 116). 

It is well known that the selective transport of ions through a mitochondrial inner membrane is attained when the oxygen supplied by the respiration oxidizes glycolysis products in mitochondria with the aid of such substances as flavin mononucleotide (FMN), fi-nicotinamide adenine dinucleotide (NADH), and quinone (Q) derivatives [1-3]. The energy that enables ion transport has been attributed to that supplied by electron transport through the membrane due to a redox reaction occurring at the aqueous-membrane interface accompanied by respiration [1-5],... 

A well-known example of active transport is the sodium-potassium pump that maintains the imbalance of Na and ions across cytoplasmic membranes. Flere, the movement of ions is coupled to the hydrolysis of ATP to ADP and phosphate by the ATPase enzyme, liberating three Na+ out of the cell and pumping in two K [21-23]. Bacteria, mitochondria, and chloroplasts have a similar ion-driven uptake mechanism, but it works in reverse. Instead of ATP hydrolysis driving ion transport, H gradients across the membranes generate the synthesis of ATP from ADP and phosphate [24-27]. 

A number of substances have been discovered in the last thirty years with a macrocyclic structure (i.e. with ten or more ring members), polar ring interior and non-polar exterior. These substances form complexes with univalent (sometimes divalent) cations, especially with alkali metal ions, with a stability that is very dependent on the individual ionic sort. They mediate transport of ions through the lipid membranes of cells and cell organelles, whence the origin of the term ion-carrier (ionophore). They ion-specifically uncouple oxidative phosphorylation in mitochondria, which led to their discovery in the 1950s. This property is also connected with their antibiotic action. Furthermore, they produce a membrane potential on both thin lipid and thick membranes. 

Ca2+ is the main intracellular signalling molecule in smooth muscle. Fluctuation in local cytoplasmic [Ca2+] near Ca2+-sensitive effector molecules allows for specific regulation of multiple functions. These temporal fluctuations and spatial variations of cytoplasmic [Ca2+] are dependent on the interactions of ion transport proteins located in the plasma membrane (PM) and membranes of the sacoplasmic reticulum (SR), nuclear envelope and mitochondria. These... 

Figure 2.8 The ATP/ADP cycle. The major ATP-generating process from fuel oxidation is oxidative phosphorylation driven by electron transport in the mitochondria. In muscle, the major energy-requiring process is physical activity. The phosphate ion is omitted from the figure for the sake of simplicity.

The transport systems of the inner mitochondrial membrane use various mechanisms. Metabolites or ions can be transported alone (uniport, U), together with a second substance (symport, S), or in exchange for another molecule (antiport. A). Active transport—i. e., transport coupled to ATP hydrolysis—does not play an important role in mitochondria. The driving force is usually the proton gradient across the inner membrane (blue star) or the general membrane potential (red star see p. 126). 

In contrast to the hydrolysis and synthesis of ATP connected with proton translocation in mitochondria, chloroplasts and bacterial membranes, the energy linked movement of calcium ions gives rise to the appearance of an acid-stable phosphorylated intermediate in the membranes. A cation specific phosphorylation also occurs in the membranes of the sodium potassium transport system183. However, due to the inability to correlate phosphorylation and ion movement in the latter membranes, membrane phosphorylation has been questioned as being a step in the reaction sequence of ion translocation184,18s. Solely the sarcoplasmic calcium transport system allows to correlate directly and quantitatively ion translocation with the phosphoryl transfer reactions. 

The mechanism of active transport is of fundamental importance in biology. As we shall see in Chapter 19, the formation of ATP in mitochondria and chloroplasts occurs by a mechanism that is essentially ATP-driven ion transport operating in reverse. The energy made available by the spontaneous flow of protons across a membrane is calculable from Equation 11-3 remember that AG for flow down an electrochemical gradient has a negative value, and AG for transport of ions against an electrochemical gradient has a positive value. 

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