scholarly journals Psychrotolerant Paenibacillus tundrae Isolates from Barley Grains Produce New Cereulide-Like Depsipeptides (Paenilide and Homopaenilide) That Are Highly Toxic to Mammalian Cells

2012 ◽  
Vol 78 (10) ◽  
pp. 3732-3743 ◽  
Author(s):  
Stiina Rasimus ◽  
Raimo Mikkola ◽  
Maria A. Andersson ◽  
Vera V. Teplova ◽  
Natalia Venediktova ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Mammalian Cells ◽  
High Performance ◽  
Food Poisoning ◽  
Respiratory Control ◽  
Structural Difference ◽  
Glucose Consumption ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Content Type

ABSTRACTPaenilide is a novel, heat-stable peptide toxin fromPaenibacillus tundrae, which colonizes barley.P. tundraeproduced 20 to 50 ng of the toxin mg−1of cells (wet weight) throughout a range of growth temperatures from +5°C to +28°C. Paenilide consisted of two substances of 1,152 Da and 1,166 Da, with masses and tandem mass spectra identical to those of cereulide and a cereulide homolog, respectively, produced byBacillus cereusNS-58. The two components of paenilide were separated from those of cereulide by high-performance liquid chromatography (HPLC), showing a structural difference suggesting the replacement ofO-Leu (cereulide) byO-Ile (paenilide). The exposure of porcine spermatozoa and kidney tubular epithelial (PK-15) cells to subnanomolar concentrations of paenilide resulted in inhibited motility, the depolarization of mitochondria, excessive glucose consumption, and metabolic acidosis. Paenilide was similar to cereulide in eight different toxicity endpoints with porcine and murine cells. In isolated rat liver mitochondria, nanomolar concentrations of paenilide collapsed respiratory control, zeroed the mitochondrial membrane potential, and induced swelling. The toxic effect of paenilide depended on its high lipophilicity and activity as a high-affinity potassium ion carrier. Similar to cereulide, paenilide formed lipocations, i.e., lipophilic cationic compounds, with K+ions already at 4 mM [K+], rendering lipid membranes electroconductive. Paenilide-producingP. tundraewas negative in a PCR assay with primers specific for thecesBgene, indicating that paenilide was not a product of plasmid pCER270, encoding the biosynthesis of cereulide inB. cereus. Paenilide represents the first potassium ionophoric compound described forPaenibacillus. The findings in this paper indicate that paenilide fromP. tundraeis a potential food-poisoning agent.

scholarly journals The maturation of the inner membrane of foetal rat liver mitochondria. An example of a positive-feedback mechanism

1975 ◽  
Vol 150 (3) ◽  
pp. 477-488 ◽  
Author(s):  
J K Pollak
Keyword(s):  
Oxidative Phosphorylation ◽  
Rat Liver ◽  
Mitochondrial Membrane ◽  
Respiratory Control ◽  
Liver Mitochondria ◽  
Neonatal Rat ◽  
Rat Liver Mitochondria ◽  
Inner Mitochondrial Membrane ◽  
Mature Adult ◽  
Foetal Rat

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.

scholarly journals Transport of reduced nicotinamide–adenine dinucleotide into mitochondria of rat white adipose tissue

1970 ◽  
Vol 116 (2) ◽  
pp. 229-233 ◽  
Author(s):  
B. H. Robinson ◽  
M. L. Halperin
Keyword(s):  
Adipose Tissue ◽  
Rat Liver ◽  
White Adipose Tissue ◽  
Nicotinamide Adenine Dinucleotide ◽  
Aspartate Aminotransferase ◽  
Respiratory Control ◽  
Liver Mitochondria ◽  
Nadh Oxidation ◽  
Rat Liver Mitochondria ◽  
Reduced Nicotinamide Adenine Dinucleotide

Mitochondria from rat white adipose tissue were prepared, exhibiting good respiratory control and P/O ratios. They would not oxidize NADH unless NNN′N′-tetramethyl-p-phenylenediamine was added as a carrier of reducing equivalents. These mitochondria were found to oxidize neither l-glycerol 3-phosphate nor l-glutamate plus l-malate at significant rates. The activity of aspartate aminotransferase in these mitochondria was found to be low compared with that found in rat liver mitochondria. As a consequence of this, the adipose-tissue mitochondria exhibited very low rates of cytoplasmic NADH oxidation in a reconstituted Borst (1962) cycle compared with liver mitochondria.

Uncoupling activity of endogenous free fatty acids in rat liver mitochondria

1978 ◽  
Vol 56 (2) ◽  
pp. 111-116 ◽  
Author(s):  
Samuel H. P. Chan ◽  
Edward Higgins Jr.
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Rat Liver ◽  
Respiratory Control ◽  
Aging Effect ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria

Changes in the respiratory control index (RCI) and ADP:O ratio were found to be related to alterations in the free fatty acids levels of rat liver mitochondria aging in 0.25 M sucrose–Tris buffer at 0 °C. Free fatty acid levels increased with time after isolation of mitochondria while a concomitant decrease in the RCI and ADP:O ratio occurred. The changes in free fatty acid levels corresponded with the reported increasing levels of phospholipase A activity in aged mitochondrial preparations. Washing these mitochondria with sucrose buffer containing 1% defatted bovine serum albumin (BSA) counteracted the aging effect on the RCI (e.g., 2.5 to 3.5) and reduced the free fatty acid levels (e.g., 50 to 16 nmol/mg protein). This reversible phenomenon could be repeated several times during the in vitro aging at 0 °C. Use of 125I-iodinated BSA showed that approximately 5 μg BSA/mg mitochondria was adsorbed by the mitochondrial membranes during washing. These results indicate a direct correlation between the level of endogenous fatty acids and the uncoupling of mitochondrial oxidative phosphorylation. The mechanism of counteracting the aging effect by BSA involves the removal of some of the free fatty acids.

Microbial toxin’s effect on mitochondrial survival by increasing K+ uptake

2009 ◽  
Vol 25 (7) ◽  
pp. 441-446 ◽  
Author(s):  
N-E. Leo Saris ◽  
Maria A Andersson ◽  
Raimo Mikkola ◽  
Leif C Andersson ◽  
Vera V Teplova ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Lipid Membranes ◽  
Neuronal Cells ◽  
Streptomyces Griseus ◽  
Atp Synthesis ◽  
Cell Types ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Black Lipid Membranes ◽  
Boar Spermatozoa

We studied the effects of toxins, which inhibited the motility of boar spermatozoa, on rat liver mitochondria. The toxins studied were originally from bacteria isolated from moisture-damaged buildings where inhabitants exhibited symptoms, or from food causing poisoning. Some strains of Bacillus cereus and Streptomyces griseus produced potassium ionophoric peptides cereulide and valinomycin (Mikkola, et al., European Journal of Biochemistry 1999; 263: 112—117). Of interest is that channels were formed in black-lipid membranes (BLM) with a selectivity of K+ > Na+ at a concentration of 26 nM. Recently, bafilomycin A1—an inhibitor of V-H+ATPases—was found also to be a K+-specific ionophore active at nanomolar concentrations (Teplova, et al., J Bioenerg Biomembr 2007; 39: 321—329), while B. amyloliquefaciens produced amylosin, a cation channel-forming peptide with a higher selectivity for K+ over Na+ at around 200 nM concentrations (Mikkola, et al., Toxicon 2007; 49: 1158—1171). Of interest is that channels were formed in BLM with a selectivity of K+ > Na+ at a concentration of 26 nM. The ionophores and the channel-forming amylosin caused swelling of energized mitochondria due to uptake of K+, loss of membrane potential, inhibition of maximal respiration rates due to loss of pyridine nucleotides, and inhibition of ATP synthesis. Various cell types may have different sensitivities to the effects of the ionophores. Thus, the mitochondrial membrane potential in neuronal cells was more sensitive to cereulide than in differentiated Paju cells (Teplova, et al., Acta Biochimica Polonica 2004; 51: 539—544). Swelling causes release of proapoptotic factors from mitochondria, which explains that undifferentiated neuronal cells were sensitive, while differentiated Paju cells were resistant, which probably is due to them having an increased expression of the antiapoptotic protein Bcl-2 and the neuroprotective stanniocalcin.

scholarly journals T-2307 Causes Collapse of Mitochondrial Membrane Potential in Yeast

2012 ◽  
Vol 56 (11) ◽  
pp. 5892-5897 ◽  
Author(s):  
Tatsuya Shibata ◽  
Toshinari Takahashi ◽  
Eio Yamada ◽  
Akiko Kimura ◽  
Hiroshi Nishikawa ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Rat Liver ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Liver Mitochondria ◽  
Yeast Cells ◽  
Rat Liver Mitochondria ◽  
Content Type ◽  
Glycerol Medium

ABSTRACTT-2307, an arylamidine compound, has been previously reported to have broad-spectrumin vitroandin vivoantifungal activities against clinically significant pathogens, includingCandidaspecies,Cryptococcus neoformans, andAspergillusspecies, and is now undergoing clinical trials. Here we investigated the mechanism of action of T-2307 using yeast cells and mitochondria isolated from yeast and rat liver. Nonfermentative growth ofCandida albicansandSaccharomyces cerevisiaein glycerol medium, in which yeasts relied on mitochondrial respiratory function, was inhibited at 0.001 to 0.002 μg/ml (0.002 to 0.004 μM) of T-2307. However, fermentative growth in dextrose medium was not inhibited by T-2307. Microscopic examination using Mitotracker fluorescent dye, a cell-permeant mitochondrion-specific probe, demonstrated that T-2307 impaired the mitochondrial function ofC. albicansandS. cerevisiaeat concentrations near the MIC in glycerol medium. T-2307 collapsed the mitochondrial membrane potential in mitochondria isolated fromS. cerevisiaeat 20 μM. On the other hand, in isolated rat liver mitochondria, T-2307 did not have any effect on the mitochondrial membrane potential at 10 mM. Moreover, T-2307 had little inhibitory and stimulatory effect on mitochondrial respiration in rat liver mitochondria. In conclusion, T-2307 selectively disrupted yeast mitochondrial function, and it was also demonstrated that the fungal mitochondrion is an attractive antifungal target.

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