scholarly journals The nature of the calcium ion efflux induced in rat liver mitochondria by the oxidation of endogenous nicotinamide nucleotides

1980 ◽  
Vol 188 (1) ◽  
pp. 113-118 ◽  
Author(s):  
D G Nicholls ◽  
M D Brand

Ca2+ efflux from rat liver mitochondria can occur when endogenous nicotinamide nucleotides are oxidized. It is suggested that nicotinamide nucleotide induced by acetoacetate sensitizes the mitochondria to damaage resulting from the accumulation of Ca2+ in the presence of Pi. Thus, acetoacetate-induced Ca2+ efflux is associated with a loss of respiratory control. Both the effluxes induced by acetoacetate and by high Ca2+ accumulation are prevented by ATP plus oligomycin, although these agents do not prevent the endoagenous nicotinamide nucleotides from becoming oxidized on addition of acetoacetate. Acetoacetate addition only results in Ca2+ release if the Ca2+ and Pi concentration are above a critical value. The acetoacetate-induced Ca2+ effflux is exactly paralled by the virtually complete collapse of the membrane potential. The presence of acetoacetate decreases the concentration of total Ca2+ necessary to induced mitochondrial damage by about 130 nmol of Ca2+/mg of protein. It is concluded that acetoacetate-induced efflux occurs by reversal of the Ca2+ uniporter after the collapse of the membrane potential.

Biochemistry ◽  
1983 ◽  
Vol 22 (26) ◽  
pp. 6341-6351 ◽  
Author(s):  
T. E. Gunter ◽  
J. H. Chace ◽  
J. S. Puskin ◽  
K. K. Gunter

2000 ◽  
Vol 203 (22) ◽  
pp. 3425-3434 ◽  
Author(s):  
A. Toninello ◽  
M. Salvi ◽  
L. Colombo

Liver mitochondria from the great green goby Zosterisessor ophiocephalus (Pallas) normally exhibit bioenergetic variables (membrane potential 165+/−7 mV; respiratory control ratio 6.6+/−0.4; ADP/O ratio 1.85+/−0.8; means +/− s.e.m., N=6) and activities of physiological transport systems (phosphate/proton symporter, adenine nucleotide antiporter, Ca(2+) electrophoretic uniporter) comparable with those of rat liver mitochondria. When incubated in the presence of Ca(2+) and an inducer agent such as phosphate, these mitochondria undergo a complete collapse of membrane potential accompanied by a large-amplitude swelling of the matrix, influx of sucrose from the incubation medium, release of endogenous Mg(2+) and K(+) (approximately 90% of the total) and of preaccumulated Ca(2+) and oxidation of endogenous pyridine nucleotides. All these phenomena, which are completely eliminated by cyclosporin A and inhibited with different efficacies by Mg(2+) and spermine, demonstrate that the induction of the permeability transition in this type of mitochondria has characteristics similar to those described in rat liver mitochondria. In contrast, the requirement for very high Ca(2+) concentrations (greater than 100 micromol l(−1) for the induction of the permeability transition represents a very important difference that distinguishes this phenomenon in fish and mammalian mitochondria.


1983 ◽  
Vol 212 (3) ◽  
pp. 773-782 ◽  
Author(s):  
B P Hughes ◽  
J H Exton

The effects of micromolar concentrations of Mn2+ on the rat liver mitochondrial Ca2+ cycle were investigated. It was found that the addition of Mn2+ to mitochondria which were cycling 45Ca2+ led to a rapid dose dependent decrease in the concentration of extramitochondrial 45Ca2+ of about 1 nmol/mg of protein. The effect was complete within 30 s, was half maximal with 10 microM Mn2+ and was observed in the presence of 3 mM Mg2+ and 1 mM ATP. It occurred over a broad range of incubation temperatures, pH and mitochondrial Ca2+ loads. It was not observed when either Mg2+ or phosphate was absent from the incubation medium, or in the presence of Ruthenium Red. These findings indicate that micromolar concentrations of Mn2+ stimulate the uptake of Ca2+ by rat liver mitochondria, and provide evidence for an interaction between Mg2+ and Mn2+ in the control of mitochondrial Ca2+ cycling.


1975 ◽  
Vol 150 (3) ◽  
pp. 477-488 ◽  
Author(s):  
J K Pollak

A new method was devised for the isolation of foetal and neonatal rat lvier mitochondria, giving higher yields than conventional methods. 2. During development from the perinatal period to the mature adult, the ratio of cytochrome oxidase/succinate-cytochrome c reductase changes. 3. The inner mitochondrial membrane of foetal liver mitochondria possesses virtually no osmotic activity; the permeability to sucrose decreases with increasing developmental age. 4. Foetal rat liver mitochondria possess only marginal respiratory control and do not maintain Ca2+-induced respiration; they also swell in respiratory-control medium in the absence of substrate. ATP enhances respiratory control and prevents swelling, adenylyl imidodiphosphate, ATP+atractyloside enhance the R.C.I. (respiratory control index), Ca2+-induced respiratory control and prevent swelling, whereas GTP and low concentrations of ADP have none of these actions. It is concluded that the effect of ATP depends on steric interaction with the inner mitochondrial membrane. 5. When 1-day pre-partum foetuses are obtained by Caesarean section and maintained in a Humidicrib for 90 min, mitochondrial maturation is ‘triggered’, so that their R.C.I. is enhanced and no ATP is required to support Ca2+-dependent respiratory control or to inhibit mitochondrial swelling. 6. It is concluded that foetal rat liver mitochondria in utero do not respire, although they are capable of oxidative phosphorylation in spite of their low R.C.I. The different environmental conditions which the neonatal rat encounters ex utero enable the hepatic mitochondria to produce ATP, which interacts with the inner mitochondrial membrane to enhance oxidative phosphorylation by an autocatalytic mechanism.


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