Metal promoted cleavage of diethylenetriamine to give β-alanine

Bernardi, R.; Zanotti, M.; Bernardi, G.; Duatti, Adriano

doi:10.1039/c39920001015

Cited by 44 publications

(55 citation statements)

References 3 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1A show that in respiring, control mitochondria accumulation of Ca 2+ from the suspension buffer followed by addition of ruthenium red (RR) and the uncoupler carbonylcyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) resulted in swelling (trace a), which was completely inhibited by CsA (trace b). This was expected since depolarization of the mitochondrial membrane when the matrix Ca 2+ concentration is high triggers opening of the PT pore, resulting in extensive diffusion of sucrose from the external medium [4]. In mitochondria pre-treated with PGO, swelling was inhibited (Fig.…”

Section: Resultsmentioning

confidence: 87%

“…Since maximal respiration was not inhibited by PGO treatment in hypotonically ruptured mitochondria (by re-suspension in 1 mM HEPES pH 7.4, results not shown), we conclude that inhibition of respiration by PGO is due to inhibition of substrate transport rather than of the respiratory chain. It must be stressed that, due to the increased probability of pore opening caused by depolarization [4,5], partial respiratory inhibition by PGO as such should have promoted rather than inhibited the PT. To test this prediction, we carried out experiments similar to those reported in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The immunosuppressive peptide cyclosporin A (CsA) inhibits the pore at nanomolar concentrations by binding to matrix cyclophilin, which may lead to its dissociation from the inner mitochondrial membrane and possibly from its putative binding sites on the pore [2,3]. The PT pore is controlled by several ligands as well as by the electric potential difference (A\|/) across the inner mitochondrial membrane; at high values of A\|/ the closed conformation prevails whereas a decrease in the A\|/ can trigger pore opening [4,5]. The pore is activated by Ca 2+ from the mitochondrial matrix and by an increase in the reduction potential of intramitochondrial pyridine nucleotides and glutathione [6,7].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of the mitochondrial cyclosporin A‐sensitive permeability transition pore by the arginine reagent phenylglyoxal

et al. 1997

View full text Add to dashboard Cite

The mitochondrial permeability transition pore, a cyclosporin A-sensitive channel, is controlled by the transmembrane electric potential difference across the inner membrane. Here, we show that treatment of rat liver mitochondria with the arginine reagent phenylglyoxal inhibits the permeability transition pore triggered by depolarization with uncoupler after Ca 2+ accumulation. Phenylglyoxal does not change the extent of mitochondrial Ca 2+ uptake or the extent of membrane depolarization, indicating that covalent modification of arginine (and possibly lysine) residues directly affects the open probability of the pore. We propose that arginine residues play a role in the physiological control of the permeability transition pore by the mitochondrial transmembrane potential.

show abstract

Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of the mitochondrial cyclosporin A‐sensitive permeability transition pore by the arginine reagent phenylglyoxal

et al. 1997

View full text Add to dashboard Cite

show abstract

“…(Fantin et al, 2002) Chemotherapy and mitochondria (Bernardi, 1992;Kowaltowski et al, 1996) Uncoupler, classical MPT inducer.…”

Section: In Vitromentioning

confidence: 99%

Mitochondria as therapeutic targets for cancer chemotherapy

et al. 2006

View full text Add to dashboard Cite

Mitochondria are vital for cellular bioenergetics and play a central role in determining the point-of-no-return of the apoptotic process. As a consequence, mitochondria exert a dual function in carcinogenesis. Cancer-associated changes in cellular metabolism (the Warburg effect) influence mitochondrial function, and the invalidation of apoptosis is linked to an inhibition of mitochondrial outer membrane permeabilization (MOMP). On theoretical grounds, it is tempting to develop specific therapeutic interventions that target the mitochondrial Achilles' heel, rendering cancer cells metabolically unviable or subverting endogenous MOMP inhibitors. A variety of experimental therapeutic agents can directly target mitochondria, causing apoptosis induction. This applies to a heterogeneous collection of chemically unrelated compounds including positively charged a-helical peptides, agents designed to mimic the Bcl-2 homology domain 3 of Bcl-2-like proteins, ampholytic cations, metals and steroid-like compounds. Such MOMP inducers or facilitators can induce apoptosis by themselves (monotherapy) or facilitate apoptosis induction in combination therapies, bypassing chemoresistance against DNA-damaging agents. In addition, it is possible to design molecules that neutralize inhibitor of apoptosis proteins (IAPs) or heat shock protein 70 (HSP70). Such IAP or HSP70 inhibitors can mimic the action of mitochondrion-derived mediators (Smac/DIABLO, that is, second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with a low isoelectric point, in the case of IAPs; AIF, that is apoptosis-inducing factor, in the case of HSP70) and exert potent chemosensitizing effects.

show abstract

“…Many different factors regulate MPT including Ca 2ϩ and ADP levels (28), matrix pH and ⌬⌿m (29,30), mitochondrial energetic status (31,32), lipid peroxidation (33), oxidative stress because of reactive oxygen species, and/or mitochondrial GSH depletion (33)(34)(35)(36). In pathological conditions, one or several of these MPT-regulating factors may contribute to altered susceptibility to MPT.…”

mentioning

confidence: 99%

Cholesterol Impairs the Adenine Nucleotide Translocator-mediated Mitochondrial Permeability Transition through Altered Membrane Fluidity

Colell¹,

Garcı́a-Ruiz

Lluis³

et al. 2003

Journal of Biological Chemistry

124

View full text Add to dashboard Cite

Mitochondrial permeability transition (MPT) has been proposed to play a key role in cell death. Downstream MPT events include the release of apoptogenic factors that sets in motion the mitochondrial apoptosome leading to caspase activation. The current work examined the regulation of MPT by membrane fluidity modulated upon cholesterol enrichment. Mitochondria enriched in cholesterol displayed increased microviscosity resulting in impaired MPT induced by atractyloside, a c-conformation stabilizing ligand of the adenine nucleotide translocator (ANT). This effect was dependent on the dose of cholesterol loaded and reversed upon the fluidization of mitochondria by the fatty acid derivative A 2 C. Mitoplasts derived from cholesterol-enriched mitochondria responded to atractyloside in a similar fashion as intact mitochondria, indicating that a significant amount of cholesterol is still found in the inner membrane. The effects of cholesterol on MPT induced by atractyloside were mirrored by the release of intermembrane proteins, cytochrome c, Smac/Diablo, and apoptosis inducing factor. However, cholesterol loading did not affect the uptake rate of adenine nucleotide hence dissociating the function of ANT as a MPT-mediated protein from its adenine nucleotide exchange function. Thus, these findings indicate that the ability of atractyloside to induce MPT via ANT requires an appropriate membrane fluidity range.

show abstract

Metal promoted cleavage of diethylenetriamine to give β-alanine

Cited by 44 publications

References 3 publications

Inhibition of the mitochondrial cyclosporin A‐sensitive permeability transition pore by the arginine reagent phenylglyoxal

Inhibition of the mitochondrial cyclosporin A‐sensitive permeability transition pore by the arginine reagent phenylglyoxal

Mitochondria as therapeutic targets for cancer chemotherapy

Cholesterol Impairs the Adenine Nucleotide Translocator-mediated Mitochondrial Permeability Transition through Altered Membrane Fluidity

Contact Info

Product

Resources

About