Modification of permeability transition pore arginine(s) by phenylglyoxal derivatives in isolated mitochondria and mammalian cells. Structure-function relationship of arginine ligands
| Autor: | Milena, Johans, Eva, Milanesi, Marina, Franck, Christoffer, Johans, Julius, Liobikas, Maria, Panagiotaki, Lucedio, Greci, Giovanni, Principato, Paavo K J, Kinnunen, Paolo, Bernardi, Paola, Costantini, Ove, Eriksson |
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| Rok vydání: | 2005 |
| Předmět: |
Time Factors
Mitochondrial Permeability Transition Pore Protein Conformation Hydrogen Bonding Mitochondria Liver Intracellular Membranes Arginine Mitochondrial Membrane Transport Proteins Phenylglyoxal Ion Channels Permeability Membrane Potentials Mitochondria Rats Models Chemical Cell Line Tumor Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Cyclosporine Animals Humans Calcium Rats Wistar Mitochondrial Swelling HeLa Cells Protein Binding |
| Zdroj: | The Journal of biological chemistry. 280(13) |
| ISSN: | 0021-9258 |
| Popis: | Methylglyoxal and synthetic glyoxal derivatives react covalently with arginine residue(s) on the mitochondrial permeability transition pore (PTP). In this study, we have investigated how the binding of a panel of synthetic phenylglyoxal derivatives influences the opening and closing of the PTP. Using both isolated mitochondria and mammalian cells, we demonstrate that the resulting arginine-phenylglyoxal adduct can lead to either suppression or induction of permeability transition, depending on the net charge and hydrogen bonding capacity of the adduct. We report that phenylglyoxal derivatives that possess a net negative charge and/or are capable of forming hydrogen bonds induced permeability transition. Derivatives that were overall electroneutral and cannot form hydrogen bonds suppressed permeability transition. When mammalian cells were incubated with low concentrations of negatively charged phenylglyoxal derivatives, the addition of oligomycin caused a depolarization of the mitochondrial membrane potential. This depolarization was completely blocked by cyclosporin A, a PTP opening inhibitor, indicating that the depolarization was due to PTP opening. Collectively, these findings highlight that the target arginine(s) is functionally linked with the opening/closing mechanism of the PTP and that the electric charge and hydrogen bonding of the resulting arginine adduct influences the conformation of the PTP. These results are consistent with a model where the target arginine plays a role as a voltage sensor. |
| Databáze: | OpenAIRE |
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