Proton gradient, in mitochondria

Although the primary role of the proton gradient in mitochondria is to furnish energy for the synthesis of ATP, the proton-motive force also drives several transport processes essential to oxidative phosphorylation. The inner mitochondrial membrane is generally impermeable to charged species, but two specific systems transport ADP and Pj into the matrix and ATP out to the cytosol (Fig. 19-26). 

DNP is a lipophilic molecule that binds reversibly with protons. It dissipates that proton gradient in mitochondria by transferring protons across the inner membrane. The uncoupling of electron transport from oxidative phosphorylation causes the energy from food to be dissipated as heat. DNP causes liver failure because of insufficient ATP synthesis in a metabolically demanding organ. 

When protons flow spontaneously down their electrochemical gradient, energy is made available to do work. In mitochondria, chloroplasts, and aerobic bacteria, the electrochemical energy in the proton gradient drives the synthesis of ATP from ADP and P,. We return to the energetics and stoichiometry of ATP synthesis driven by the electrochemical potential of the proton gradient in Section 19.2. 

The biotin-dependent decarboxylases of anerobic microorganisms are transmembrane proteins. In addition to their roles in the metabolism of ox-aloacetate, methylmalonyl CoA, and glutaconyl CoA, they serve as energy transducers. They transport 2 mol of sodium out of the cell for each mole of substrate decarboxylated. The resultant sodium gradient is then used for active transport of substrates by sodium cotranspoit systems, or maybe used to drive ATP synthesis in a similar manner to the proton gradient in mammalian mitochondria (Buckel, 2001). 

Nicholls D.G. (1978) Calcium transport and proton electrochemical potential potential gradient in mitochondria from guinea-pig cerebral cortex and rat heart. Biochem. J. 170 511 —22. 

When Mitchell first described his chemiosmotic hypothesis in 1961, little evidence existed to support it, and it was met with considerable skepticism by the scientific community. Eventually, however, considerable evidence accumulated to support this model. It is now clear that the electron transport chain generates a proton gradient, and careful measurements have shown that ATP is synthesized when a pH gradient is applied to mitochondria that cannot carry out electron transport. Even more relevant is a simple but crucial experiment reported in 1974 by Efraim Racker and Walther Stoeckenius, which provided specific confirmation of the Mitchell hypothesis. In this experiment, the bovine mitochondrial ATP synthasereconstituted in simple lipid vesicles with bac-teriorhodopsin, a light-driven proton pump from Halobaeterium halobium. As shown in Eigure 21.28, upon illumination, bacteriorhodopsin pumped protons... 

When isolated mitochondria are incubated with substrate, Pj, and oxygen, in the absence of ADP (state 4, Chance and Williams, 1956), the proton gradient is not dissipated and electron transport is slow since the redox potential is balanced by the PMF. Addition of ADP (State 3, Chance and Williams, 1956) stimulates... 

Recent studies by Crompton et al. have shown that oxidant stress may open a Ca-sensitive, non-selective pore in the inner mitochondrial membrane that is blocked by cyclosporin A (Crompton, 1990 Crompton and Costi, 1990). This pore opening results in massive mitochondrial swelling, dissipation of the transmembrane proton gradient and disruption of mitochondrial energy production (Crompton et al., 1992). Since mitochondria may play a role as a slow, high-capacity cytosolic calcium buffer (Isenberg et al., 1993), disruption of mitochondrial function may also contribute to calcium overload and cell injury. 

The chemi-osmotic theory of oxidative phosphorylation has been reviewed,74 a model for mitochondrial oxidative phosphorylation in which a membrane potential or proton gradient might transmit energy from an oxidation step to ATP synthesis has been proposed,76 and adenine nucleotide transport in mitochondria has been reviewed.76... 

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