Mitochondrial membrane potential

Atovaquone, a hydroxynaphthoquinone, selectively inhibits the respiratory chain of protozoan mitochondria at the cytochrome bcl complex (complex III) by mimicking the natural substrate, ubiquinone. Inhibition of cytochrome bcl disrupts the mitochondrial electron transfer chain and leads to a breakdown of the mitochondrial membrane potential. Atovaquone is effective against all parasite stages in humans, including the liver stages. 

Nicholls, DG and Ward, MW (2000) Mitochondrial membrane potential and neuronal glutamate excitotoxicity mortality and millivolts. Trends Neurosci. 23 166-174. 

The involvement of mitochondria in the pro-apoptotic effects of carotenoids has been clearly demonstrated by the fact that P-carotene induces the release of cytochrome c from mitochondria and alters the mitochondrial membrane potential (Aym) in different tumor cells (Palozza et al., 2003a). Moreover, the highly polar xanthophyll neoxanthin has been reported to induce apoptosis in colon cancer cells by a mechanism that involves its accumulation into the mitochondria and a consequent loss of mitochondrial transmembrane potential and releas of cytochrome c and apoptosis-inducing factor (Terasaki et al., 2007). 

Mitochondrial Membrane Potential Detection of metalloproteinase activity Cell metabolism Yes [32]... 

S. Tada-Oikawa, Y. Hiraku, M. Kawanishi, and S. Kawanishi, Mechanism for generation of hydrogen peroxide and change of mitochondrial membrane potential during rotenone-induced apoptosis. Life Sci. 73, 3277-3288 (2003). 

As in the case of superoxide production by prooxidant enzymes described in Chapter 22, reliable data on mitochondrial superoxide production have been received by the use of lucigenin-amplified CL [12]. Lucigenin cation easily accumulates in mitochondria with the negative mitochondrial membrane potential and is able to penetrate the inner membrane of mitochondria. Therefore, this method permits to measure superoxide production by the whole mitochondria and mitochondrial superoxide production in cells. For example, Esterline and Trush [13] registered a significant lucigenin-amplified CL produced by the mitochondria of unstimulated rat alveolar macrophages that cannot be due to the activity of dormant NADPH oxidase. 

As a rule, oxygen radical overproduction in mitochondria is accompanied by peroxidation of mitochondrial lipids, glutathione depletion, and an increase in other parameters of oxidative stress. Thus, the enhancement of superoxide production in bovine heart submitochondrial particles by antimycin resulted in a decrease in the activity of cytochrome c oxidase through the peroxidation of cardiolipin [45]. Iron overload also induced lipid peroxidation and a decrease in mitochondrial membrane potential in rat liver mitochondria [46]. Sensi et al. [47] demonstrated that zinc influx induced mitochondrial superoxide production in postsynaptic neurons. 

FIGURE 31-7 Mitochondrial carriers. Ions and small molecules enter the intermembrane space, since the outer mitochondrial membrane is not a significant permeability barrier. However, the inner mitochondrial membrane is impermeable to ions except those for which there are specific carriers. Most of the carriers are reversible, as indicated by two-headed arrows. Compounds transported in one direction are indicated in red. The ATP/ADP translocase and the aspartate-glutamate carrier are both electrophoretic their transport is driven in the direction of the mitochondrial membrane potential, as indicated by red arrows. Glutamine is carried into the matrix by an electroneutral carrier. The unimpaired functioning of mitochondrial carriers is essential for normal metabolism. (Adapted with permission from reference [70].)... 

Intracellular Enzymes Stem Cell Isolation Cellular Membrane Potential Mitochondrial Membrane Potential Gene Reporter Assay Gene Silencing (siRNA)... 

Mitochondria are distinct organelles with two membranes. The outer membrane limits the organelle and the inner membrane is thrown into folds or shelves that project inward and are called cristae mitochondriales. The uptake of most mitochondrion-selective dyes is dependent on the mitochondrial membrane potential. Conventional fluorescent stains for mitochondria, such as rhodamine and tetramethylrosamine, are readily sequestered by functioning mitochondria. They are, however, subsequently washed out of the cells once the mitochondrion s membrane potential is lost. This characteristic limits their use in experiments in which cells must be treated with aldehyde-based fixatives or other agents that affect the energetic state of the mitochondria. To overcome this limitation, the research... 

Smiley ST, Reers M, Mottola-Hartshom C, Lin M, Chen A, Smith TW, Steele GD Jr, Chen LB (1991) Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1. Proc Natl Acad Sci USA 88 3671-3675... 

Quick K, Dugan L (2004) Fullerene derivative (C ) functions as a SOD mimetic by reducing age-related increase in superoxide levels and prevention of age-related loss of mitochondrial membrane potential in brain. Free Rad. Biol. Med. 37 S163-S163. 

Li, P.F., Dietz, R., and von Harsdorf, R., 1999, P53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochrome c-independent apoptosis blocked by Bcl-2, EMBO J. 18 66027-6036. 

A dissipation of mitochondrial membrane potential (A P/w) is often detectable dining apoptosis (Green, 1998 Shidoji et al, 1997). A loss of A Pm is thonght to be mediated by the opening of the mitochondrial permeability transition pore which is proposed to be involved in mitochondrial efflux of cytochrome c into the cytosol (Scarlett and Mnrphy, 1997). However, a recent report by Bossy-Wetzel et al (1998) provided... 

Schluter, T., Struy, H., and Schonfeld P., 2000, Protection of mitochondrial integrity from oxidative stress by the triaminopyridine derivative flupirtine. FEBS Lett., 481 42-46 Shidoji, Y., Nakamura, N., Moriwaki, H., and Muto, Y., 1997, Rapid loss in the mitochondrial membrane potential during geranygeranoic acid-induced apoptosis. 

Strategies for the design of mitochondria-targeted drug and DNA delivery systems and the principles such systems are based upon have been reviewed earlier by us comprehensively (16-18). Therefore, the scope of this chapter shall be limited exclusively to approaches involving mitochondriotropic molecules-mediated drug and DNA delivery to mammalian mitochondria in response to the mitochondrial membrane potential. 

Oxidative phosphorylation DNP, potassium cyanide Antimycin A Sodium azide Formaldehyde Uncouples the oxidative phosphorylation from electron transport Acts at cytochrome oxidase B 7 Decreases the mitochondrial membrane potential 105 101,102 93,101,102... 

Formaldehyde treatment with low concentrations of formaldehyde can lead to a series of effects, one example being the decrease in mitochondrial membrane potential and the inhibition of mitochondrial respiration. 

Furthermore, since the cell growth arrest is often linked to cell death. The annexin V staining positive cell or the amount of DNA fragmentation assessed by TUNEL and FACS analysis has been interpreted as indicative of apoptosis. The HDACI-induced apoptosis can also be determined by Western blotting of target proteins, detection of mitochondrial membrane potentials, activation of caspases and their substrate cleavages in a dose- and time-dependent manner. 

For example, mitochondrial reductive capacity is decreased with decreased cell numbers but is increased with cells that are activated, such as lymphocytic immune activation, or if cells adapt to the stress associated with toxicity, such as during mitochondrial biogenesis. Thus, mitochondrial reductive capacity might be either increased or decreased with toxicity. Similar contradictory interpretations might occur with other cellular activities, for which there is a compensatory adaptive increase before their failure. This biphasic change is referred to as hormesis and occurs not only with reductive mitochondrial activity but also with mitochondrial number, cell number, mitochondrial membrane potential, antioxidant system activity and numerous other activities. 

Permeability transition pore Opening by reactive oxygen species, reactive nitrogen species, bile adds, ihio crosslinkers, atractyloside, betu-liniate, lonidamidem various anticancer drugs, to collapse mitochondrial membrane potential and activate mitochondrial apoptotic pathway... 

Dye oxidation (e.g., tetrazolium reductase activity with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, MTT 2-[4-iodophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H tetrazolium monosodium salt, WST-1 3- (4,5 -carboxymethoxyphenyl) -2-(4-sulfophenyl)-2 H-tetra-zolium, MTS 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt, XTT 2,2 -di-p-nitrophenyl-5,5 -diphenyl-3,3 -(3,3 -dimethoxy-4,4 -diphe-nylenej-ditetrazolium chloride, NET), Alamar blue assays, ATP concentration (e.g., luciferase assay), oxygen consumption (e.g., oxygen electrodes, phosphorescent oxygen-sensitive dyes), mitochondrial protein and nucleic acid synthesis mitochondrial mass (e.g., mitotracker dyes) mitochondrial membrane potential (e.g., tetramethylrho-damine methyl ester, TMRM tetramethylrhodamine ethyl ester, TMRE)... 

Haasio, K. et al. (2002) Effects of entacapone and tolcapone on mitochondrial membrane potential. European Journal of Pharmacology, 453 (1), 21-26. 

Dykens, J.A. and Stout, A.K. (2001) Fluorescent dyes and assessment of mitochondrial membrane potential in FRET Modes. Fluorescent dyes and assessment of mitochondrial membrane potential in FRET modes. Methods in Cell Biology, 65, 285-309. 

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