Bidirectional fluxes of spermine across the mitochondrial membrane

Grancara, Silvia; Martinis, Pamela; Manente, Sabrina; García-Argáez, Aída Nelly; Tempera, Giampiero; Bragadin, Marcantonio; Via, Lisa Dalla; Agostinelli, Enzo; Toninello, Antonio

doi:10.1007/s00726-013-1591-0

Cited by 17 publications

(10 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, conjunction with PAs may result in agents capable of selectively exploiting the highly active PA-transporters (PAT) in cancer cells (27). In addition, the PA backbone would recognize the ionic surface of mitochondria and penetrate these organelles (28). Both properties render PA–CAM conjugates promising anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol

et al. 2014

View full text Add to dashboard Cite

Chloramphenicol (CAM) is a broad-spectrum antibiotic, limited to occasional only use in developed countries because of its potential toxicity. To explore the influence of polyamines on the uptake and activity of CAM into cells, a series of polyamine–CAM conjugates were synthesized. Both polyamine architecture and the position of CAM-scaffold substitution were crucial in augmenting the antibacterial and anticancer potency of the synthesized conjugates. Compounds 4 and 5, prepared by replacement of dichloro-acetyl group of CAM with succinic acid attached to N4 and N1 positions of N8,N8-dibenzylspermidine, respectively, exhibited higher activity than CAM in inhibiting the puromycin reaction in a bacterial cell-free system. Kinetic and footprinting analysis revealed that whereas the CAM-scaffold preserved its role in competing with the binding of aminoacyl-tRNA 3′-terminus to ribosomal A-site, the polyamine-tail could interfere with the rotatory motion of aminoacyl-tRNA 3′-terminus toward the P-site. Compared to CAM, compounds 4 and 5 exhibited comparable or improved antibacterial activity, particularly against CAM-resistant strains. Compound 4 also possessed enhanced toxicity against human cancer cells, and lower toxicity against healthy human cells. Thus, the designed conjugates proved to be suitable tools in investigating the ribosomal catalytic center plasticity and some of them exhibited greater efficacy than CAM itself.

show abstract

Section: Introductionmentioning

confidence: 99%

Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Also the effects of polyamines on the conductance of larger pores like OmpF [ 26 , 29 ] and the translocase of the outer chloroplast membrane Toc75 have been tested [ 32 ]. A potential physiological role of spermine flux across the mitochondrial membranes is summarized in [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Oep23 forms an ion channel in the chloroplast outer envelope

et al. 2015

View full text Add to dashboard Cite

BackgroundMetabolite, ion and protein translocation into chloroplasts occurs across two membranes, the inner and the outer envelope. Solute and metabolite channels fulfill very important functions in integrating the organelles into the metabolic network of the cell. However so far only a few have been identified. Here we describe the identification and the characterization of the outer envelope protein of 23 kDa, Oep23 from garden pea.ResultsOep23 is found in the entire plant lineage from green algae to flowering plants. It is expressed in all organs and developmental states tested so far. The reconstituted recombinant protein Oep23 from pea forms a high conductance ion channel with a maximal conductance in the fully open state of 466 ± 14pS at a holding potential of +100 mV (in 250 mM KCl). The Oep23 channel is cation selective (PK+ : PCl- = 15 : 1) with a voltage dependent open probability of maximal Vmem = 0 mV.ConclusionThe data indicate that the Oep23 activity represents a single channel unit and does not assemble into a multiple pore complex like bacterial type porins or mitochondrial voltage dependent anion channel. Thus, Oep23 represents a new member of ion channels in the outer envelope of chloroplasts involved in solute exchange.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-015-0445-1) contains supplementary material, which is available to authorized users.

show abstract

“…Polyamines interact with mitochondrial membranes at specific sites involved in their electrophoretic transport in mitochondria (Grancara et al 2014). In particular, spermine can also flow from organelles by promoting the crossmembrane cycling which regulates the induction of MPT (Agostinelli et al 2010).…”

Section: Mitochondria As Targets Of "Mitochondrial Medicine"mentioning

confidence: 99%

Pathophysiological implications of mitochondrial oxidative stress mediated by mitochondriotropic agents and polyamines: the role of tyrosine phosphorylation

et al. 2015

Self Cite

View full text Add to dashboard Cite

Mitochondria, once merely considered as the "powerhouse" of cells, as they generate more than 90 % of cellular ATP, are now known to play a central role in many metabolic processes, including oxidative stress and apoptosis. More than 40 known human diseases are the result of excessive production of reactive oxygen species (ROS), bioenergetic collapse and dysregulated apoptosis. Mitochondria are the main source of ROS in cells, due to the activity of the respiratory chain. In normal physiological conditions, ROS generation is limited by the anti-oxidant enzymatic systems in mitochondria. However, disregulation of the activity of these enzymes or interaction of respiratory complexes with mitochondriotropic agents may lead to a rise in ROS concentrations, resulting in oxidative stress, mitochondrial permeability transition (MPT) induction and triggering of the apoptotic pathway. ROS concentration is also increased by the activity of amine oxidases located inside and outside mitochondria, with oxidation of biogenic amines and polyamines. However, it should also be recalled that, depending on its concentration, the polyamine spermine can also protect against stress caused by ROS scavenging. In higher organisms, cell signaling pathways are the main regulators in energy production, since they act at the level of mitochondrial oxidative phosphorylation and participate in the induction of the MPT. Thus, respiratory complexes, ATP synthase and transition pore components are the targets of tyrosine kinases and phosphatases. Increased ROS may also regulate the tyrosine phosphorylation of target proteins by activating Src kinases or phosphatases, preventing or inducing a number of pathological states.

show abstract

Bidirectional fluxes of spermine across the mitochondrial membrane

Cited by 17 publications

References 42 publications

Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol

Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol

Oep23 forms an ion channel in the chloroplast outer envelope

Pathophysiological implications of mitochondrial oxidative stress mediated by mitochondriotropic agents and polyamines: the role of tyrosine phosphorylation

Contact Info

Product

Resources

About